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Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks? | Infection
<!DOCTYPE html> <html lang="en" class="no-js"> <head> <meta charset="UTF-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta name="robots" content="max-image-preview:large"> <meta name="access" content="Yes"> <meta name="360-site-verification" content="1268d79b5e96aecf3ff2a7dac04ad990" /> <title>Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks? | Infection </title> <meta name="twitter:site" content="@SpringerLink"/> <meta name="twitter:card" content="summary_large_image"/> <meta name="twitter:image:alt" content="Content cover image"/> <meta name="twitter:title" content="Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?"/> <meta name="twitter:description" content="Infection - Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dichotomy between pro- and..."/> <meta name="twitter:image" content="https://media.springernature.com/full/springer-static/cover-hires/journal/15010"/> <meta name="journal_id" content="15010"/> <meta name="dc.title" content="Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?"/> <meta name="dc.source" content="Infection 2020 49:1"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Springer"/> <meta name="dc.date" content="2020-12-23"/> <meta name="dc.type" content="ReviewPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2020 The Author(s)"/> <meta name="dc.rights" content="2020 The Author(s)"/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dichotomy between pro- and eukaryotic pathways with high affinities of agents to bacterial- rather than eukaryotic targets. However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes. This review summarizes data describing multiple modes of action of antibiotics in eukaryotes. Aminoglycosides, macrolides, oxazolidinones, chloramphenicol, clindamycin, tetracyclines, glycylcyclines, fluoroquinolones, rifampicin, bedaquillin, ß-lactams inhibited mitochondrial translation either due to binding to mitosomes, inhibition of mitochondrial RNA-polymerase-, topoisomerase 2ß-, ATP-synthesis, transporter activities. Oxazolidinones, tetracyclines, vancomycin, ß-lactams, bacitracin, isoniazid, nitroxoline inhibited matrix-metalloproteinases (MMP) due to chelation with zinc and calcium, whereas fluoroquinols&nbsp;fluoroquinolones and chloramphenicol chelated with these cations, too, but increased MMP activities. MMP-inhibition supported clinical efficacies of ß-lactams and daptomycin in skin-infections, and of macrolides, tetracyclines in respiratory-diseases. Chelation may have contributed to neuroprotection by ß-lactams and fluoroquinolones. Aminoglycosides, macrolides, chloramphenicol, oxazolidins&nbsp;oxazolidinones, tetracyclines caused read-through of premature stop codons. Several additional targets for antibiotics in human cells have been identified like interaction of fluoroquinolones with DNA damage repair in eukaryotes, or inhibition of mucin overproduction by oxazolidinones. The effects of antibiotics on eukaryotes are due to identical mechanisms as their antibacterial activities because of structural and functional homologies of pro- and eukaryotic targets, so that the effects of antibiotics on mammals are integral parts of their overall mechanisms of action."/> <meta name="prism.issn" content="1439-0973"/> <meta name="prism.publicationName" content="Infection"/> <meta name="prism.publicationDate" content="2020-12-23"/> <meta name="prism.volume" content="49"/> <meta name="prism.number" content="1"/> <meta name="prism.section" content="ReviewPaper"/> <meta name="prism.startingPage" content="29"/> <meta name="prism.endingPage" content="56"/> <meta name="prism.copyright" content="2020 The Author(s)"/> <meta name="prism.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="prism.url" content="https://link.springer.com/article/10.1007/s15010-020-01536-y"/> <meta name="prism.doi" content="doi:10.1007/s15010-020-01536-y"/> <meta name="citation_pdf_url" content="https://link.springer.com/content/pdf/10.1007/s15010-020-01536-y.pdf"/> <meta name="citation_fulltext_html_url" content="https://link.springer.com/article/10.1007/s15010-020-01536-y"/> <meta name="citation_journal_title" content="Infection"/> <meta name="citation_journal_abbrev" content="Infection"/> <meta name="citation_publisher" content="Springer Berlin Heidelberg"/> <meta name="citation_issn" content="1439-0973"/> <meta name="citation_title" content="Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?"/> <meta name="citation_volume" content="49"/> <meta name="citation_issue" content="1"/> <meta name="citation_publication_date" content="2021/02"/> <meta name="citation_online_date" content="2020/12/23"/> <meta name="citation_firstpage" content="29"/> <meta name="citation_lastpage" content="56"/> <meta name="citation_article_type" content="Review"/> <meta name="citation_fulltext_world_readable" content=""/> <meta name="citation_language" content="en"/> <meta name="dc.identifier" content="doi:10.1007/s15010-020-01536-y"/> <meta name="DOI" content="10.1007/s15010-020-01536-y"/> <meta name="size" content="1038593"/> <meta name="citation_doi" content="10.1007/s15010-020-01536-y"/> <meta name="citation_springer_api_url" content="http://api.springer.com/xmldata/jats?q=doi:10.1007/s15010-020-01536-y&api_key="/> <meta name="description" content="Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dich"/> <meta name="dc.creator" content="Dalhoff, Axel"/> <meta name="dc.subject" content="Infectious Diseases"/> <meta name="dc.subject" content="General Practice / Family Medicine"/> <meta name="dc.subject" content="Internal Medicine"/> <meta name="citation_reference" content="citation_journal_title=Nat Rev Drug Discov; citation_title=Paul Ehrlich: founder of chemotherapy; citation_author=SHE Kaufmann; citation_volume=7; citation_publication_date=2008; citation_pages=373; citation_doi=10.1038/nrd2582; citation_id=CR1"/> <meta name="citation_reference" content="Bäumler E (1997) Paul Ehrlich, Forscher für das Leben. 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However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes. Methods and objective This review summarizes data describing multiple modes of action of antibiotics in eukaryotes. Results Aminoglycosides, macrolides, oxazolidinones, chloramphenicol, clindamycin, tetracyclines, glycylcyclines, fluoroquinolones, rifampicin, bedaquillin, ß-lactams inhibited mitochondrial translation either due to binding to mitosomes, inhibition of mitochondrial RNA-polymerase-, topoisomerase 2ß-, ATP-synthesis, transporter activities. Oxazolidinones, tetracyclines, vancomycin, ß-lactams, bacitracin, isoniazid, nitroxoline inhibited matrix-metalloproteinases (MMP) due to chelation with zinc and calcium, whereas fluoroquinols fluoroquinolones and chloramphenicol chelated with these cations, too, but increased MMP activities. MMP-inhibition supported clinical efficacies of ß-lactams and daptomycin in skin-infections, and of macrolides, tetracyclines in respiratory-diseases. Chelation may have contributed to neuroprotection by ß-lactams and fluoroquinolones. Aminoglycosides, macrolides, chloramphenicol, oxazolidins oxazolidinones, tetracyclines caused read-through of premature stop codons. Several additional targets for antibiotics in human cells have been identified like interaction of fluoroquinolones with DNA damage repair in eukaryotes, or inhibition of mucin overproduction by oxazolidinones. Conclusion The effects of antibiotics on eukaryotes are due to identical mechanisms as their antibacterial activities because of structural and functional homologies of pro- and eukaryotic targets, so that the effects of antibiotics on mammals are integral parts of their overall mechanisms of action."/> <meta property="og:image" content="https://media.springernature.com/full/springer-static/cover-hires/journal/15010"/> <meta name="format-detection" content="telephone=no"> <link rel="apple-touch-icon" sizes="180x180" href=/oscar-static/img/favicons/darwin/apple-touch-icon-92e819bf8a.png> <link rel="icon" type="image/png" sizes="192x192" href=/oscar-static/img/favicons/darwin/android-chrome-192x192-6f081ca7e5.png> <link rel="icon" type="image/png" sizes="32x32" href=/oscar-static/img/favicons/darwin/favicon-32x32-1435da3e82.png> <link rel="icon" type="image/png" sizes="16x16" href=/oscar-static/img/favicons/darwin/favicon-16x16-ed57f42bd2.png> <link rel="shortcut icon" 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However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes. This review summarizes data describing multiple modes of action of antibiotics in eukaryotes. Aminoglycosides, macrolides, oxazolidinones, chloramphenicol, clindamycin, tetracyclines, glycylcyclines, fluoroquinolones, rifampicin, bedaquillin, ß-lactams inhibited mitochondrial translation either due to binding to mitosomes, inhibition of mitochondrial RNA-polymerase-, topoisomerase 2ß-, ATP-synthesis, transporter activities. Oxazolidinones, tetracyclines, vancomycin, ß-lactams, bacitracin, isoniazid, nitroxoline inhibited matrix-metalloproteinases (MMP) due to chelation with zinc and calcium, whereas fluoroquinols fluoroquinolones and chloramphenicol chelated with these cations, too, but increased MMP activities. MMP-inhibition supported clinical efficacies of ß-lactams and daptomycin in skin-infections, and of macrolides, tetracyclines in respiratory-diseases. Chelation may have contributed to neuroprotection by ß-lactams and fluoroquinolones. Aminoglycosides, macrolides, chloramphenicol, oxazolidins oxazolidinones, tetracyclines caused read-through of premature stop codons. Several additional targets for antibiotics in human cells have been identified like interaction of fluoroquinolones with DNA damage repair in eukaryotes, or inhibition of mucin overproduction by oxazolidinones. The effects of antibiotics on eukaryotes are due to identical mechanisms as their antibacterial activities because of structural and functional homologies of pro- and eukaryotic targets, so that the effects of antibiotics on mammals are integral parts of their overall mechanisms of action.","datePublished":"2020-12-23T00:00:00Z","dateModified":"2020-12-23T00:00:00Z","pageStart":"29","pageEnd":"56","license":"http://creativecommons.org/licenses/by/4.0/","sameAs":"https://doi.org/10.1007/s15010-020-01536-y","keywords":["Selective toxicity","Eukaryotic targets","Mitochondria","Metallo-matrix proteinases","Read through","DNA damage repair","Helicases","Neuroprotection","Infectious Diseases","General Practice / Family Medicine","Internal Medicine"],"image":[],"isPartOf":{"name":"Infection","issn":["1439-0973","0300-8126"],"volumeNumber":"49","@type":["Periodical","PublicationVolume"]},"publisher":{"name":"Springer Berlin Heidelberg","logo":{"url":"https://www.springernature.com/app-sn/public/images/logo-springernature.png","@type":"ImageObject"},"@type":"Organization"},"author":[{"name":"Axel Dalhoff","url":"http://orcid.org/0000-0001-9371-5838","affiliation":[{"name":"Institue for Infection Medicine","address":{"name":"Christian-Albrechts-University of Kiel, Institue for Infection Medicine, Kiel, Germany","@type":"PostalAddress"},"@type":"Organization"}],"email":"adalhoff@t-online.de","@type":"Person"}],"isAccessibleForFree":true,"@type":"ScholarlyArticle"},"@context":"https://schema.org","@type":"WebPage"}</script> </head> <body class="" > <!-- Google Tag Manager (noscript) --> <noscript> <iframe src="https://www.googletagmanager.com/ns.html?id=GTM-MRVXSHQ" height="0" width="0" style="display:none;visibility:hidden"></iframe> </noscript> <!-- End Google Tag Manager (noscript) --> <!-- Google Tag Manager (noscript) --> <noscript data-test="gtm-body"> <iframe 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antibacterial agents—still a valid concept or do we miss chances and ignore risks? </div> <div data-test="inCoD" data-track-context="sticky banner"> <div class="c-pdf-container"> <div class="c-pdf-download u-clear-both u-mb-16"> <a href="/content/pdf/10.1007/s15010-020-01536-y.pdf" class="u-button u-button--full-width u-button--primary u-justify-content-space-between c-pdf-download__link" data-article-pdf="true" data-readcube-pdf-url="true" data-test="pdf-link" data-draft-ignore="true" data-track="content_download" data-track-type="article pdf download" data-track-action="download pdf" data-track-label="button" data-track-external download> <span class="c-pdf-download__text">Download PDF</span> <svg aria-hidden="true" focusable="false" width="16" height="16" class="u-icon"><use xlink:href="#icon-eds-i-download-medium"/></svg> </a> </div> </div> </div> </div> </div> <div class="c-article-header"> <header> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Axel-Dalhoff-Aff1" data-author-popup="auth-Axel-Dalhoff-Aff1" data-author-search="Dalhoff, Axel" data-corresp-id="c1">Axel Dalhoff<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><span class="u-js-hide"> <a class="js-orcid" href="http://orcid.org/0000-0001-9371-5838"><span class="u-visually-hidden">ORCID: </span>orcid.org/0000-0001-9371-5838</a></span><sup class="u-js-hide"><a href="#Aff1">1</a></sup> </li></ul> <div data-test="article-metrics"> <ul class="app-article-metrics-bar u-list-reset"> <li class="app-article-metrics-bar__item"> <p class="app-article-metrics-bar__count"><svg class="u-icon 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class="app-article-metrics-bar__details"><a href="/article/10.1007/s15010-020-01536-y/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Explore all metrics <svg class="u-icon app-article-metrics-bar__arrow-icon" width="24" height="24" aria-hidden="true" focusable="false"> <use xlink:href="#icon-eds-i-arrow-right-medium"></use> </svg></a></p> </li> </ul> </div> <div class="u-mt-32"> </div> </header> </div> <div data-article-body="true" data-track-component="article body" class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Background</h3><p>Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dichotomy between pro- and eukaryotic pathways with high affinities of agents to bacterial- rather than eukaryotic targets. However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Methods and objective</h3><p>This review summarizes data describing multiple modes of action of antibiotics in eukaryotes.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Results</h3><p>Aminoglycosides, macrolides, oxazolidinones, chloramphenicol, clindamycin, tetracyclines, glycylcyclines, fluoroquinolones, rifampicin, bedaquillin, ß-lactams inhibited mitochondrial translation either due to binding to mitosomes, inhibition of mitochondrial RNA-polymerase-, topoisomerase 2ß-, ATP-synthesis, transporter activities. Oxazolidinones, tetracyclines, vancomycin, ß-lactams, bacitracin, isoniazid, nitroxoline inhibited matrix-metalloproteinases (MMP) due to chelation with zinc and calcium, whereas fluoroquinols fluoroquinolones and chloramphenicol chelated with these cations, too, but increased MMP activities. MMP-inhibition supported clinical efficacies of ß-lactams and daptomycin in skin-infections, and of macrolides, tetracyclines in respiratory-diseases. Chelation may have contributed to neuroprotection by ß-lactams and fluoroquinolones. Aminoglycosides, macrolides, chloramphenicol, oxazolidins oxazolidinones, tetracyclines caused read-through of premature stop codons. Several additional targets for antibiotics in human cells have been identified like interaction of fluoroquinolones with DNA damage repair in eukaryotes, or inhibition of mucin overproduction by oxazolidinones.</p><h3 class="c-article__sub-heading" data-test="abstract-sub-heading">Conclusion</h3><p>The effects of antibiotics on eukaryotes are due to identical mechanisms as their antibacterial activities because of structural and functional homologies of pro- and eukaryotic targets, so that the effects of antibiotics on mammals are integral parts of their overall mechanisms of action.</p></div></div></section> <div data-test="cobranding-download"> </div> <section aria-labelledby="inline-recommendations" data-title="Inline Recommendations" class="c-article-recommendations" data-track-component="inline-recommendations"> <h3 class="c-article-recommendations-title" id="inline-recommendations">Similar content being viewed by others</h3> <div class="c-article-recommendations-list"> <div class="c-article-recommendations-list__item"> <article class="c-article-recommendations-card" itemscope itemtype="http://schema.org/ScholarlyArticle"> <div class="c-article-recommendations-card__img"><img src="https://media.springernature.com/w215h120/springer-static/image/art%3Aplaceholder%2Fimages/placeholder-figure-springernature.png" loading="lazy" alt=""></div> <div class="c-article-recommendations-card__main"> <h3 class="c-article-recommendations-card__heading" itemprop="name headline"> <a class="c-article-recommendations-card__link" itemprop="url" href="https://link.springer.com/10.1007/s15010-020-01547-9?fromPaywallRec=false" data-track="select_recommendations_1" data-track-context="inline recommendations" data-track-action="click recommendations inline - 1" data-track-label="10.1007/s15010-020-01547-9">Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets? 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He defined antibacterial agents as “substances with an exclusive affinity for bacteria acting deleteriously or lethally on these alone, while at the same time, they possess no affinity for the normal constituents of the body…” [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Kaufmann SHE. Paul Ehrlich: founder of chemotherapy. Nat Rev Drug Discov. 2008;7:373. 
 https://doi.org/10.1038/nrd2582
 
 . " href="#ref-CR1" id="ref-link-section-d32404569e445">1</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Bäumler E (1997) Paul Ehrlich, Forscher für das Leben. Edition Wötzel, Frankfurt am Main, dritte durchgesehene Auflage, dritter Teil: Der Weg zur Chemotherapie, 1997; pp 161–192. ISBN 3-925831-21-5" href="#ref-CR2" id="ref-link-section-d32404569e445_1">2</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Gradmann C. Magic bullets and moving targets: antibiotic resistance and experimental chemotherapy, 1900–1940. Dynamis. 2011;31:305–21. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR3" id="ref-link-section-d32404569e448">3</a>]. The selective toxicity of ß-lactams, for example, is considered to be due to their affinity to penicillin binding proteins (PBPs) and inhibition of biosynthesis of bacterial cell walls, both being unique to prokaryotes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 4" title="Stewart GT. Toxicity of the penicillins. Postgrad Med J. 1964;40(Suppl):160–5. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR7" id="ref-link-section-d32404569e461">7</a>]. Thus, antibacterial agents interact specifically with targets either being unique to bacteria or being characterized by a dichotomy between pro- and eukaryotic pathways with high affinities of agents to the bacterial- rather than eukaryotic target.</p><p>However, it is well documented that aminoglycosides [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Dalhoff A (1987) Pleiotropic actions of aminoglycosides. In: Döring G, Holder IA, Botzenhart K (eds). Basic Research and Clinical Aspects of Pseudomonas aeruginosa. International Symposium on Pseudomonas aeruginosa, Tübingen, June 1986. Antibiot Chemother. Basel, Karger, vol 39, pp 182–204 
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 " href="/article/10.1007/s15010-020-01536-y#ref-CR8" id="ref-link-section-d32404569e467">8</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 9" title="Cohen JI. New activities of old aminoglycosides. Nat Microbiol. 2018;3:531–2. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR9" id="ref-link-section-d32404569e470">9</a>], fluoroquinolones [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 10" title="Dalhoff A. Antiviral, antifungal, and antiparasitic activities of fluoroquinols optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action? Eur J Clin Microbiol Infect Dis. 2015;34:661–8. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR10" id="ref-link-section-d32404569e473">10</a>], tetracyclines [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 11" title="Griffin MO, Fricovsky E, Ceballos G, Villarreal F. Tetracyclines: a pleiotropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010a;299:C539–48. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR12" id="ref-link-section-d32404569e479">12</a>], macrolides [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 13" title="Wong EHC, Porter JD, Edwards MR, Johnston SL. The role of macrolides in asthma: current evidence and future directions. Lancet Respir Med. 2014;2:657–70. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR13" id="ref-link-section-d32404569e483">13</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 14" title="Min JY, Jang YJ. Macrolide therapy in respiratory viral infections. Mediators Inflamm. 2012. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR14" id="ref-link-section-d32404569e486">14</a>], and even ß-lactams [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 15" title="Hamilton-Miller JMT. ß-lactams: variations on a chemical theme, with some surprising biological results. J Antimicrob Chemother. 1999;44:729–34. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR16" id="ref-link-section-d32404569e492">16</a>], optimized for treatment of bacterial infections exert antiviral-, antifungal-, antiparasitic-, and/or antineoplastic effects. It is difficult to comprehend that a monocausal activity relationship allows enough flexibility for such polypharmacological effects. It has been demonstrated that e.g. aminoglycosides [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Kotra LP, Haddad J, Mobashery S. Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob Agents Chemother. 2000;44:3249–56. 
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 . " href="#ref-CR18" id="ref-link-section-d32404569e495_1">18</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 19" title="Tekos A, Tsagla A, Stathopoulos C, Drainas D. Inhibition of eukaryotic ribonuclease P activity by aminoglycosides: kinetic studies. FEBS Lett. 2000;485:71–5. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR19" id="ref-link-section-d32404569e498">19</a>] and tetracyclines [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Chuckwudi C. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob Agents Chemother. 2016;60:4433–41. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR20" id="ref-link-section-d32404569e502">20</a>] bind to a variety of targets. Such alternative binding sites may help to explain the pleiotropic actions of antibacterial agents against pro- and/or eukaryotic organisms.</p><p>The interaction of antibacterial agents (antibiotics in the following) with mammalian targets is known since long. The discovery of hypoglycaemic sulfonamides can be attributed to the observation in 1942 that treatment of typhoid fever with the sulphonamide 2254RP caused hypoglycaemia in some patients [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 21" title="Loubatieres-Mariani MM. The discovery of hypoglycemic sulphonamides. J Soc Biol. 2007;20:121–5. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR21" id="ref-link-section-d32404569e508">21</a>]. A number of sulfonamides are used in the treatment of protozoal infections in animals and humans. In addition, immunomodulatory activities in particular of macrolides [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 22" title="Altenburg J, De Graaff CS, Van Der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics–par 1: biological mechanisms. Respiration. 2011;81:67–74. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR22" id="ref-link-section-d32404569e511">22</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 23" title="Labro MT, Abdelghaffar H. Immunomodulation by macrolide antibiotics. J Chemother. 2001;13:3–8. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR23" id="ref-link-section-d32404569e514">23</a>], fluoroquinolones [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 24" title="Dalhoff A, Shalit I. Immunomodulatory effects of quinols. Lancet Infect Dis. 2003;3:359–71. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR24" id="ref-link-section-d32404569e517">24</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 25" title="Dalhoff A. Immunomodulatory activities of fluoroquinols. Infection. 2005;33:55–70. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR25" id="ref-link-section-d32404569e520">25</a>], and almost every other drug class [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 26" title="Labro T. Interference of antibacterial agents with phagocyte functions: immunomodulation or “immuno-fairy tales”? Clin Microbiol Rev. 2000;13:615–50. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR27" id="ref-link-section-d32404569e527">27</a>] demonstrate that antibiotics affect eukaryotic cells, too, probably due to a physicochemical interaction with membranes thus triggering intracellular signaling cascades in pro- and eukaryotes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 28" title="Dalhoff A (2018) Membrane interactions of antibacterial agents. Trend Clin Microbiol 1: 04–48. 
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 " href="/article/10.1007/s15010-020-01536-y#ref-CR28" id="ref-link-section-d32404569e530">28</a>], so that interspecies and interkingdom communication is affected [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Petra AI, Panagiotidou S, Hatziagelaki E, Stewart M, Conti P, Theoharides TC. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther. 2015;37:984–95. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR32" id="ref-link-section-d32404569e536">32</a>]. These examples indicate the paradigm of selective toxicity is oversimplified. Instead, agents interfere with multiple targets in pro- as well as eukaryotic cells due to compound- and target promiscuity [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Hu Y, Gupta-Ostermann D, Bajorath J. Exploring compound promiscuity patterns and multi-target activity spaces. Computat Structural Biotechnol J. 2014;9:e201401003. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR35" id="ref-link-section-d32404569e543">35</a>] and target homology as will be demonstrated below.</p><p>This review summarizes data describing multiple modes of action of antibiotics and is limited exclusively to a synopsis of studies describing interactions of antibiotics with pro- and eukaryoric targets although the clinical condition may be complex and multifactorial. Thus, clinical improvement may result from pleiotropic actions of an antibiotic which, however, should not be mentioned as this review is focussed on the targets. Only those agents are mentioned which are used clinically for treatment of bacterial infections; their structural derivatives optimized for non-antiinfective activities will not be discussed. Phenotypic descriptions of drug effects will not be discussed either. Comprehensive reviews have aggregated a plethora of data describing the phenotypes of action of polyfunctional antibiotics [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Brown D. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void? Nature Rev Drug Discovery. 2015;14:821–32. 
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 . " href="#ref-CR37" id="ref-link-section-d32404569e549_1">37</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Ratcliff WC, Denison RF. Alternative actions for antibiotics. Science. 2011;332:547–8. 
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 . " href="#ref-CR38" id="ref-link-section-d32404569e549_2">38</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Pasquale TR, Tan JS. Nonantimicrobial effects of antibacterial agents. Clin Infect Dis. 2005;40:127–35. 
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 . " href="#ref-CR40" id="ref-link-section-d32404569e549_4">40</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Kalayci J. Antimicrobial properties of various non-antimicrobial drugs against microorganisms. Bioanal Biomed. 2016;8:4. 
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 . " href="#ref-CR41" id="ref-link-section-d32404569e549_5">41</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 42" title="Kruszewska H, Zareba T, Tyski S. Search of antimicrobial activity of selected non-antibiotic drugs. Acta Pol Pharm. 2002;59:436–9 ((PMID: 12669766)). " href="/article/10.1007/s15010-020-01536-y#ref-CR42" id="ref-link-section-d32404569e552">42</a>]. The reader is kindly referred to these summaries for further information. Adverse drug reactions, drug/drug interactions, and indirect effects mediated by oxidant scavenging activities, immunomodulation, and beneficial- or detrimental effects resulting from microbiome imbalance, etc. will not be discussed either. To emphasize a priori, most of the therapeutic opportunities mentioned below have not been reviewed by regulatory authorities and the preclinical and/or clinical evidence supporting these potential novel indications varies widely. The majority of preclinical studies were planned as hypothesis generating experiments and most clinical studies have been designed as retrospective observational rather than prospective, randomized clinical studies. But still these data suggest that therapeutic options of an antibiotic treatment may likely be more diverse than expected.</p></div></div></section><section data-title="Non-antimicrobial activities of antibiotics beyond structural and mechanistic boundaries"><div class="c-article-section" id="Sec2-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec2">Non-antimicrobial activities of antibiotics beyond structural and mechanistic boundaries</h2><div class="c-article-section__content" id="Sec2-content"><p>Detailed information about non-antimicrobial actions of antibiotics is provided in the supplemental material. Data compiled in Tables S1 and S2 confirm that antibiotics of almost every drug class interact with cellular- and in particular mitochondrial functions like autophagy and apoptosis/caspase mediated proteolysis as well as activities of matrix metalloproteinases (MMPs) thus exerting pleiotropic effects including anti-neoplastic activities. However, review and analysis of published data is difficult, since four variables had a significant impact on the data generated. First, the use of different methods results in divergent outcomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 43" title="Hanemaaijer R, van Lent N, Sorsa T, Salo T, Yrj Ö, Konttinen T, Lindemann J. Inhibition of matrix metalloproteinases (MMPs) by tetracyclines. In: Nelson M, Hillen W, Greenwald RA, editors. Tetracyclines in Biology, Chemistry and Medicine. Basel: Birkhäuser; 2001. 
 https://doi.org/10.1007/978-3-0348-8306-1_11
 
 ((Print ISBN 978-3-0348-9511-8)). " href="/article/10.1007/s15010-020-01536-y#ref-CR43" id="ref-link-section-d32404569e563">43</a>]. Second, antibiotics affected cellular functions also indirectly via interaction with cytokines and/or signaling cascades. Such systems are frequently redundant and pleomorph. Many cytokines are synthesized by more than one cell and different cells may secrete different cytokines with dissimilar activities and different stimuli may trigger diverse effects [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 24" title="Dalhoff A, Shalit I. Immunomodulatory effects of quinols. Lancet Infect Dis. 2003;3:359–71. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR24" id="ref-link-section-d32404569e566">24</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 25" title="Dalhoff A. Immunomodulatory activities of fluoroquinols. Infection. 2005;33:55–70. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR25" id="ref-link-section-d32404569e569">25</a>]. Consequently, indirect effects of antibiotics on cellular functions via immunomodulation are not uniform but differ according to cell lines used and targets studied. Three examples should be mentioned pars pro toto: azithromycin and moxifloxacin decreased respiratory epithelial cell derived MMP1 and -3 concentrations, whereas both agents increased MMP secretion from MRC-5 fibroblasts [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 44" title="Singh S, Kubler A, Singh UK, Singh A, Gardiner H, Prasad R, Elkington PT, Friedland JS. Antimycobacterial drugs modulate immunopathogenic matrix metalloproteinases in a cellular model of pulmonary tuberculosis. Antimicrob Agents Chemother. 2014;58:4657–65. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR45" id="ref-link-section-d32404569e581">45</a>]. IC<sub>50</sub>-values of azithromycin for inhibition of proliferation and induction of apoptosis in HeLa-, cervical- and gastric cancer cells were 15.66, 26.05 and 91.00 mg/L [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 46" title="Zhou X, Zhang Y, Li Y, Hao X, Liu X, Wang Y. Azithromycin synergistically enhances anti-proliferative activity of vincristine in cervical and gastric cancer cells. Cancers. 2012;4:1318–32. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR46" id="ref-link-section-d32404569e586">46</a>]. Third, the parameter measured is not necessarily congruent to the mode of action of an antibiotic. Rifampicin and para-aminosalicylic acid, for example, inhibited secretion of MMPs secondary to an inhibition of prostaglandin synthesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 47" title="Yuhas Y, Azoulay-Alfaguter I, Berent E, Ashkenazi S. Rifampin inhibits prostaglandin E2 production and arachidonic acid release in human alveolar epithelial cells. Antimicrob Agents Chemother. 2007;51:4225–30. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR48" id="ref-link-section-d32404569e592">48</a>], so that these antibiotics targeted the endocrine system but not MMP synthesis. Fourth, antibiotic concentrations used in in vitro experiments scatter over a broad range and were frequently unphysiologically high. However, humanized doses were administered to experimental animals and standard doses were used in clinical studies on e.g. anti-neoplastic effects of antibiotics – even in monotherapy—or inhibition of MMP activities. For example, pancreatic cancer cell lines were exposed to 400 mg/L each of ciprofloxacin, moxifloxacin, and gatifloxacin; their maximal serum concentrations following oral standard doses are as low as 2.3-, 5.0-, and 3.8 mg/L [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 49" title="Yadav V, Varshney P, Sultana S, Yadav J, Saini N. Moxifloxacin and ciprofloxacin induces S-phase arrest and augments apoptotic effects of cisplatin in human pancreatic cancer cells via ERK activation. BMC Cancer. 2015;15:581. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR74" id="ref-link-section-d32404569e624">74</a>]. Data summarized in Table S1 demonstrate that cancer cell growth was affected by aminoglycosides, macrolides, tetracyclines, oxazolidinones, chloramphenicol, clindamycin, rifampicin targeting mitochondrial translation, quinolones targeting mitochondrial topoisomerases, and bedaquilin targeting mitochondrial ATP-synthesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 75" title="Luo M, Zhou W, Patel H, Srivastava AP, Symerdky J, Bonar MM, Feraldo-Gomez JD, Liao M, Mueller DM. Bedaquiline inhibits the yeast and human mitochondrial ATP synthases. Commun Biol. 2020;3:452. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR75" id="ref-link-section-d32404569e627">75</a>]. However, the mitochondrial membrane may constitute a permeation barrier thus explaining that oxazolidinones, chloramphenicol and tetracyclines were significant inhibitors, while macrolides, clindamycin and aminoglycosides were poor inhibitors of mitochondrial protein synthesis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 68" title="McKee EE, Ferguson M, Bentley AT, Marks TA. Inhibition of mammalian mitochondrial protein synthesis by oxazolidins. Antimicrob Agents Chemother. 2006;50:2042–9. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR68" id="ref-link-section-d32404569e631">68</a>]. Beta-lactams affected mitochondrial functions due to inhibition of carnitine/acylcarnitine transporter (Table S1). In addition, the agents also affected signaling cascades, micro-RNAs, and acted as immunomodulators or anti-inflammatory agents, so that antineoplastic activities of antibiotics may be due to interactions with multiple targets. Clinical trials indicated that aminoglycosides, macrolides, tetracyclines and fluoroquinolones, clarithromycin, and ciprofloxacin in particular, reduced mortalities in cancer patients, even as mono-therapeutics [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Van Nuffel AM, Sukhatme V, Pantziarka P, Meheus L, Sukhatme VP, Bouche G. Repurposing Drugs in Oncology (ReDO)—clarithromycin as an anti-cancer agent. Ecancermedicalscience. 2015. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR5" id="ref-link-section-d32404569e822">5</a>]. The D-Ala-D-Ala building block as well as the structure of the bacterial cell wall is considered to be unique to prokaryotes. Consequently, PBPs and class A, C, and D ß-lactamases being acyl serine transferases are considered to be bacteria specific [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 156" title="Goffin C, Ghuysen JM. Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol Mol Biol Rev. 1998;62:1079–93 ((PMID: 9841666)). " href="/article/10.1007/s15010-020-01536-y#ref-CR156" id="ref-link-section-d32404569e825">156</a>]. But structural homologies between bacterial- and human serine proteases are conceivable as eukaryotic acyl serine transferases like trypsin, thrombin, etc. transfer the electrophilic group of e.g. peptide carbonyl donors to an acceptor. The carbonyl donor is transpeptidated with the acceptor when the acceptor carries an aminogroup – as happens in the course of cell wall biosynthesis. Most of the approximately 1,000 bacterial serine proteases like the D-Ala-D-Ala carboxypeptidases are single domain proteases in prokaryotes with functional specialisation [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 157" title="Tripathi LP, Sowdhamini R. Genome-wide survey of prokaryotic serine proteases: analysis of distribution and domain architectures of five serine protease families in prokaryotes. BMC Genomics. 2008;9:549. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR219" id="ref-link-section-d32404569e954">219</a>]. Translation, elongation and termination are altered in a manner that induced read-through of premature stop codons (PTCs) (<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Palmer E, Wilhelm JM, Sherman F. Phenotypic suppression of nonsense mutants in yeast by aminoglycoside antibiotics. Nature. 1979;277:148–50. https://doi.org/10.1038/277148a0." href="#ref-CR220" id="ref-link-section-d32404569e957">220</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Lee HL, Dougherty JP. Pharmaceutical therapies to recode nonsense mutations in inherited diseases. Pharmacol Ther. 2012;136:227–66. 
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 . " href="#ref-CR221" id="ref-link-section-d32404569e957_1">221</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 222" title="Manuvakhova M, Keeling K, Bedwell DM. Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translationsystem. RNA. 2000;6:1044–55. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR222" id="ref-link-section-d32404569e961">222</a>, and Table S1). These findings have led to their consideration as potent drugs to treat human diseases caused by PTCs [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 221" title="Lee HL, Dougherty JP. Pharmaceutical therapies to recode nonsense mutations in inherited diseases. Pharmacol Ther. 2012;136:227–66. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR221" id="ref-link-section-d32404569e964">221</a>]. Although the modes of action of aminoglycosides on eukaryotic ribosomes and their potential clinical efficacy in treatment of non-infectious diseases has been elucidated quite recently [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Palmer E, Wilhelm JM, Sherman F. Phenotypic suppression of nonsense mutants in yeast by aminoglycoside antibiotics. Nature. 1979;277:148–50. https://doi.org/10.1038/277148a0." href="#ref-CR220" id="ref-link-section-d32404569e967">220</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Lee HL, Dougherty JP. Pharmaceutical therapies to recode nonsense mutations in inherited diseases. Pharmacol Ther. 2012;136:227–66. 
 https://doi.org/10.1016/j.pharmthera.2012.07.007
 
 . " href="#ref-CR221" id="ref-link-section-d32404569e967_1">221</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 222" title="Manuvakhova M, Keeling K, Bedwell DM. Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translationsystem. RNA. 2000;6:1044–55. 
 https://doi.org/10.1017/S1355838200000716
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR222" id="ref-link-section-d32404569e970">222</a>], their efficacies in treatment of genetic disorders has been described phenotypically already in 1985, so that many data could be accumulated. Comprehensive recent reviews demonstrate that aminoglycoside-induced mutation suppression has not only been confirmed in a variety of preclinical in vitro and in vivo models but translates also into the clinical arena [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Keeling KM, Xue X, Gunn G, Bedwell DM. Therapeutics based on stop codon readthrough. Annu Rev Genomics Hum Genet. 2014;15:371–94. 
 https://doi.org/10.1146/annurev-genom-091212-153527
 
 . " href="#ref-CR223" id="ref-link-section-d32404569e973">223</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Malik V, Rodino-Klapac LR, Violett L, Mendell JR. Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy. Ther Adv Neurol Disorders. 2010;3:379–89. 
 https://doi.org/10.1177/17562856120388693
 
 . " href="#ref-CR224" id="ref-link-section-d32404569e973_1">224</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Nagel-Wolfrum K, Möller F, Penner I, Baasov T, Wolfrum U. Targeting nonsense mutations in diseases with translational read-through-inducing drugs (TRIDs). BioDrugs. 2016;30:49–74. 
 https://doi.org/10.1007/s40259-016-0157-6
 
 . " href="#ref-CR225" id="ref-link-section-d32404569e973_2">225</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 226" title="Dabrowski M, Bukowy-Bieryllo Z, Zietkiewicz E. Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons. Mol Med. 2018;24:25. 
 https://doi.org/10.1186/s10020-018-0024-7
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR226" id="ref-link-section-d32404569e976">226</a>] (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s15010-020-01536-y#Tab1">1</a>). Gentamicin, the investigational agents geneticin (G-418) and G-418 derivatives were the most frequently studied aminoglycosides; tobramycin, amikacin, paromomycin, neomycin, sisomycin, kanamycin, lividomycin, and hygromycinB were evaluated as well. While the major gentamicin compnts lack read-through activity the minor compnts, B1, X1, and G-418 caused read-through of PTCs [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 227" title="Baradaran-Heravi A, Niesser J, Balgi AD, Choi K, Zimmerman C, South AP, Anderson HJ, Strynadka NC, Bally MB, Roberge M. Gentamicin B1 is a minor gentamicin compnt with major nonsense mutation suppression activity. Proc Nat Acad Sci. 2017;114:3479–84. 
 https://doi.org/10.1073/pnas.1620982114
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR227" id="ref-link-section-d32404569e983">227</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 228" title="Friesen WJ, Johnson B, Sierra J, Zhuo J, Vazirani P, Xue X, Tomizawa Y, Baiazitov R, Morrill C, Ren H, Babu S, Moon YC, Branstrom A, Mollin A, Hedrick J, Sheedy J, Elfring G, Weetall M, Colacino JM, Welch EM, Peltz SW. The minor gentamicin complex compnt, X2, is a potent premature stop codon readthrough molecule with therapeutic potential. PLoS One . 2018;13:e0206158. 
 https://doi.org/10.1371/journal.pone.0206158
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR228" id="ref-link-section-d32404569e986">228</a>]. Aminoglycosides were initially used clinically as read-through agents in particular in the treatment of cystic fibrosis patients but concerns over the safety profile of aminoglycosides led to a search for alternatives.</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-1"><figure><figcaption class="c-article-table__figcaption"><b id="Tab1" data-test="table-caption">Table 1 Translational read-through studies</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/article/10.1007/s15010-020-01536-y/tables/1" aria-label="Full size table 1"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>Several specific features possibly limit the use of aminoglycosides in the treatment of genetic disorders: First, the identity of the stop codon and second, the sequence context surrounding it have an impact on the aminoglycoside mediated readthrough [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 222" title="Manuvakhova M, Keeling K, Bedwell DM. Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translationsystem. RNA. 2000;6:1044–55. 
 https://doi.org/10.1017/S1355838200000716
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR222" id="ref-link-section-d32404569e1643">222</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Howard MT, Shirts BH, Petros LM, Flanigan KM, Gesteland RF, Atkins JF. Sequence specificity of aminoglycoside-induced stop codon readthrough: Potential implications for treatment of Duchenne muscular dystrophy. Ann Neurol. 2000;48:164–9. 
 https://doi.org/10.1002/1531-8249(200008)48:2%3c164::AID-ANA5%3e3.0.CO;2-B
 
 . " href="#ref-CR229" id="ref-link-section-d32404569e1646">229</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Bidou L, Hatin I, Perez N, Allamand V, Panthier JJ, Rousset JP. Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment. Gene Ther. 2004;11:619–27. 
 https://doi.org/10.1038/sj.gt.3302211
 
 . " href="#ref-CR230" id="ref-link-section-d32404569e1646_1">230</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Floquet C, Hatin I, Rousset JP, Bidou L. Statistical analysis of readthrough levels for nonsense mutations in mammalian cells reveals a major determinant of response to gentamicin. PLoS One Genet. 2012;8:e1002608. https://doi.org/10.1371/journal.pgen.1002608." href="#ref-CR231" id="ref-link-section-d32404569e1646_2">231</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Dabrowski M, Bukowy-Bieryllo Z, Zietkiewicz E. Translational readthrough potential of natural termination codons in eucaryotes—the impact of RNA sequence. RNA Biol. 2015;12:950–8. 
 https://doi.org/10.1080/15476286.2015.1068497
 
 . " href="#ref-CR232" id="ref-link-section-d32404569e1646_3">232</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 233" title="Goodenough E, Robinson TM, Zook MB, Flanigan KM, Atkins JF, Howard MT, Eisenlohr LC. Cryptic MHC class I-binding peptides are revealed by aminoglycoside-induced stop codon read-through into the 3′ UTR. Proc Nat Acad Sci. 2014;111:5670–5. 
 https://doi.org/10.1073/pnas.1402670111
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR233" id="ref-link-section-d32404569e1649">233</a>], so that aminoglycosides can not suppress PTCs equally well in all patients, thus probably necessitating individualized diagnostic procedures. Third, mitochondrial dysfunction may occur in patients with specific polymorphisms in their 12S rRNA [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 234" title="Hobbie SN, Akshay S, Kalapala SK, Bruell CM, Shcherbakov D, Böttger EC. Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity. Proc Nat Acad Sci. 2008;105:20888–93. 
 https://doi.org/10.1073/pnas.0811258106
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR234" id="ref-link-section-d32404569e1652">234</a>]. Fourth, aminoglycosides impair cell respiration leading to a superoxide overproduction. Furthermore, oxidative damage of mitochondrial aconitase leads to an accumulation of free ferrous iron in mitochondria, so that ultimately cells undergo apoptosis via the Fenton reaction (<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 235" title="Shulman E, Belakhov V, Wei G, Kendall A, Meyron-Holtz EG, Ben-Shachar D, Schacht J, Baasov T. Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity a strategy for the treatment of genetic diseases. J Biol Chem. 2014;289:2318–30. 
 https://doi.org/10.1074/jbc.M113.533588
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR235" id="ref-link-section-d32404569e1655">235</a>).</p><h3 class="c-article__sub-heading" id="Sec9">Macrolides</h3><p>Macrolides inhibit protein synthesis by binding to the bacterial ribosome in the region of the nascent peptide exit tunnel. Binding of a macrolide in the exit tunnel obstructs the passage of the nascent peptides, so that overall protein synthesis rapidly declines and peptidyl-tRNAs are accumulated. Therefore, it was previously suggested that macrolides inhibit the production of cellular polypeptides completely by preventing the exit of nascent peptide chains. Recent findings revealed that macrolides, instead of directly binding to the peptidyl transferase centre and disrupting its structure, bind in the exit tunnel one or more nanometres from the peptidyl transferase centre, so that the diameter of the exit tunnel is decreased. This results in steric clashes with nascent peptides leading to a stalling of ribosome function. Despite the narrowing of the exit tunnel sufficient room is still left, so that some proteins may bypass the narrowed exit tunnel and become partially or fully synthesized, while other proteins cannot bypass the obstruction. Inhibition of protein synthesis by macrolides depends on the properties of the polypeptide being synthesized by the drug-bound ribosome. The ability to bypass is not dependent on the entire sequence of the synthesized protein, but rather on its N-terminal sequence. In addition/or other mechanisms may cause differential impacts of macrolides on protein synthesis. Perturbed conformation of rRNAs in the P-site, which can lead to a decrease in translation rate, or reorientation of rRNAs might affect the stereochemistry of the A-site thereby preventing peptide bond formation [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Nguyen HL, Pham DL, O’Brien EP, Li MS. Erythromycin leads to differential protein expression through differences in electrostatic and dispersion interactions with nascent proteins. Sci Rep. 2018;8:6460. 
 https://doi.org/10.1038/s41598-018-24344-9
 
 . " href="#ref-CR236" id="ref-link-section-d32404569e1666">236</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Kannan K, Kanabar P, Schryer D, Florin T, Oh E, Bahroos N, Tenson T, Weissman JS, Mankin AS. The general mode of translation inhibition by macrolide antibiotics. Proc Nat Acad Sci. 2014;111:15958–63. 
 https://doi.org/10.1073/pnas.1417334111
 
 . " href="#ref-CR237" id="ref-link-section-d32404569e1666_1">237</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Vázquez-Laslop N, Mankin AS. How macrolide antibiotics work. Trends Biochem Sci. 2018;43:668–84. 
 https://doi.org/10.1016/j.tibs.2018.06.011
 
 . " href="#ref-CR238" id="ref-link-section-d32404569e1666_2">238</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Vázquez-Laslop N, Ramu H, Klepacki D, Kannan K, Mankin AS. The key function of a conserved and modified rRNA residue in the ribosomal response to the nascent peptide. EMBO J. 2010;29:3108–17. 
 https://doi.org/10.1038/emboj.2010.180
 
 . " href="#ref-CR239" id="ref-link-section-d32404569e1666_3">239</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Kannan K, Vázquez-Laslop N, Mankin AS. Selective protein synthesis by ribosomes with a drug-obstructed exit tunnel. Cell. 2012;151:508–20. 
 https://doi.org/10.1016/j.cell.2012.09.018
 
 . " href="#ref-CR240" id="ref-link-section-d32404569e1666_4">240</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 241" title="Davis AR, Gohara DW, Yap MNF. Sequence selectivity of macrolide-induced translational attenuation. Proc Nat Acad Sci. 2014;111:15379–84. 
 https://doi.org/10.1073/pnas.1410356111
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR241" id="ref-link-section-d32404569e1669">241</a>]. Macrolides stall not only the ribosome within specific sequence contexts, but also induce translation errors [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 238" title="Vázquez-Laslop N, Mankin AS. How macrolide antibiotics work. Trends Biochem Sci. 2018;43:668–84. 
 https://doi.org/10.1016/j.tibs.2018.06.011
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR238" id="ref-link-section-d32404569e1672">238</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 242" title="Thompson J, Pratt CA, Dahlberg AE. Effects of a number of classes of 50S inhibitors on stop codon readthrough during protein synthesis. Antimicrob Agents Chemother. 2004;48:4889–91. 
 https://doi.org/10.1128/AAC.48.12.4889-4891.2004
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR242" id="ref-link-section-d32404569e1675">242</a>]. This effect is probably due to an inhibition of peptide bond formation and/or peptide release. This event could in turn alter kinetics of translation resulting in an increased chance of read-through. All the 14-membered and 16-membered lactone ring macrolides caused an extensive stop codon read-through of PTCs in the in vitro system studied [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 242" title="Thompson J, Pratt CA, Dahlberg AE. Effects of a number of classes of 50S inhibitors on stop codon readthrough during protein synthesis. Antimicrob Agents Chemother. 2004;48:4889–91. 
 https://doi.org/10.1128/AAC.48.12.4889-4891.2004
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR242" id="ref-link-section-d32404569e1678">242</a>] (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s15010-020-01536-y#Tab1">1</a>). In addition, macrolides can also stimulate ribosomal frameshifting, which, however, is linked to resistance mechanisms [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 233" title="Goodenough E, Robinson TM, Zook MB, Flanigan KM, Atkins JF, Howard MT, Eisenlohr LC. Cryptic MHC class I-binding peptides are revealed by aminoglycoside-induced stop codon read-through into the 3′ UTR. Proc Nat Acad Sci. 2014;111:5670–5. 
 https://doi.org/10.1073/pnas.1402670111
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR233" id="ref-link-section-d32404569e1685">233</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 237" title="Kannan K, Kanabar P, Schryer D, Florin T, Oh E, Bahroos N, Tenson T, Weissman JS, Mankin AS. The general mode of translation inhibition by macrolide antibiotics. Proc Nat Acad Sci. 2014;111:15958–63. 
 https://doi.org/10.1073/pnas.1417334111
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR237" id="ref-link-section-d32404569e1688">237</a>] and thus not relevant in the context of this review.</p><p>Read-through activities of macrolides were recorded in eukaryotes although only bacterial- or mitochondrial ribosomes are susceptible to macrolides, whereas ribosomes isolated from archaea or eukaryotic cytoplasmic ribosomes are resistant [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Douthwaite S, Hansen LH, Mauvais P. Macrolide-ketolide inhibition of MLS-resistant ribosomesis improved by alternative drug interaction with domain II of 23S rRNA. Mol Microbiol. 2000;36:183–93. 
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 . " href="#ref-CR243" id="ref-link-section-d32404569e1694">243</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Xiong L, Korkhin Y, Mankin AS. Binding site of the bridged macrolides in the Escherichia coliribosome. Antimicrob Agents Chemother. 2005;49:281–8. 
 https://doi.org/10.1128/AAC.49.1.281-288.2005
 
 . " href="#ref-CR244" id="ref-link-section-d32404569e1694_1">244</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Bommakanti AS, Lindahl L, Zengel JM. Mutation from guanine to adenine in 25S rRNA at the position equivalent to E. coli A2058 does not confer erythromycin sensitivity in Sacchromyces cerevisae. RNA. 2008;14:460–4. 
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 . " href="#ref-CR245" id="ref-link-section-d32404569e1694_2">245</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 246" title="Mathis A, Wild P, Boettger EC, Kapel CM, Deplazes P. Mitochondrial ribosome as the target for the macrolide antibiotic clarithromycin in the helminth Echinococcus multilocularis. Antimicrob Agents Chemother. 2005;49:3251–5. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR246" id="ref-link-section-d32404569e1697">246</a>]. If read-through in eukaryotes is due to an interference with mitochondrial functions only has not been addressed. Nevertheless, a clinical study investigating the efficacy of erythromycin treatment for read-through of APC gene stop codon mutations in familial adenomatous polyposis has been initiated [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 247" title="Roll M (2014) Erythromycin treatment for readthrough of APC genes top codon mutations in familial adenomatous polyposis. ClinicalTrials.gov Identifier: NCT02175914" href="/article/10.1007/s15010-020-01536-y#ref-CR247" id="ref-link-section-d32404569e1700">247</a>] and the impact of macrolides on stop codon read-through has been proven in pro- and eukaryotic species as well as patients (Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s15010-020-01536-y#Tab1">1</a>) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 242" title="Thompson J, Pratt CA, Dahlberg AE. Effects of a number of classes of 50S inhibitors on stop codon readthrough during protein synthesis. Antimicrob Agents Chemother. 2004;48:4889–91. 
 https://doi.org/10.1128/AAC.48.12.4889-4891.2004
 
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 . " href="#ref-CR251" id="ref-link-section-d32404569e1710_3">251</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Kariv R, Caspi M, Fliss-Isakov N, Shroer Y, Shor Y, Rosner G, Brazowski E, Beer G, Cohen S, Rosin-Arbesfeld R. Resorting the function of the colorectal cancer gatekeeper adenomatous polyopsis coli. Int J Cancer. 2020;146:1064–74. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR253" id="ref-link-section-d32404569e1713">253</a>].</p><p>Furthermore, macrolides are prokinetic agents due to their motilin receptor stimulating activities. Fourteen- and 15- but not 16 membered macrolides act as motilin receptor agonists. Erythromycin affects two different pathways; at a low dose (40 mg) it activates an intrinsic cholinergic pathway, whereas higher doses (200–350 mg) act on motilin receptors on enteric nerves and smooth muscle [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Catnach SM, Fairclough PD. Erythromycin and the gut. Gut. 1992;33:397–401. 
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 . " href="#ref-CR254" id="ref-link-section-d32404569e1719">254</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Coulie B, Tack J, Peeters T, Janssens J. Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans. Gut. 1998;43:395–400. 
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 . " href="#ref-CR255" id="ref-link-section-d32404569e1719_1">255</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Deloose E, Vos R, Janssen P, Van den Bergh O, Van Oudenhove L, Depoortere I, Tack J. The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway. Am J Clin Nutr. 2016;103:730–7. 
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 . " href="#ref-CR256" id="ref-link-section-d32404569e1719_2">256</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Doherty WL, Winter B. Prokinetic agents in critical care. Crit Care. 2003;7:206–8. 
 https://doi.org/10.1186/cc1849
 
 . " href="#ref-CR257" id="ref-link-section-d32404569e1719_3">257</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 258" title="Chini P, Toskes PP, Waseem S, Hou W, McDonald R, Moshiree B. Effect of azithromycin on small bowel motility in patients with gastrointestinal dysmotility. Scand J Gastroenterol. 2012;47:422–7. 
 https://doi.org/10.3109/00365521.2012.654402
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR258" id="ref-link-section-d32404569e1722">258</a>]. Erythromycin itself exerts almost no prokinetic activity but its antibacterially inactive degradation intermediate 8,9-anhydro-6,9-hemiketal serves as a motilin receptor agonist and is then further metabolized into erythromycin-6,9;9,12-spiroketal [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 259" title="Galligan JJ, Vanner S. Basic and clinical pharmacology of new motility promoting agents. Neurogastroenterol Motil. 2005;17:643–53. 
 https://doi.org/10.1111/j.1365-2982.2005.00675.x
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR259" id="ref-link-section-d32404569e1725">259</a>]. The disadvantages of the use of macrolides as prokinetic agents are that motilin-induced contractions induce hunger feelings through a cholinergic pathway [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 256" title="Deloose E, Vos R, Janssen P, Van den Bergh O, Van Oudenhove L, Depoortere I, Tack J. The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway. Am J Clin Nutr. 2016;103:730–7. 
 https://doi.org/10.3945/ajcn.115.113456
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR256" id="ref-link-section-d32404569e1728">256</a>] and that macrolide-resistance might develop.</p><p>Another target for macrolides in eukaryotes has been described recently. Roxithromycin inhibited the cellular differentiation of the rice blast fungus <i>Magnaporthe oryzae</i> [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 260" title="Ishii A, Kumasaka M, Nagashima Y, Nakajima Y, Kuramochi K, Sugawara F, Narukawa M, Kamakura T. A eukaryotic molecular target candidate of roxithromycin: fungal differentiation as a sensitive drug target analysis system. Biosci Biotechnol Biochem. 2013;77:1539–47. 
 https://doi.org/10.1271/bbb.13021
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR260" id="ref-link-section-d32404569e1737">260</a>]. The gene <i>mocdc27</i> (<i>M. oryzae</i> Cell Division Cycle 27) encoding appressorium formation is involved in growth inhibition of the fungus by roxithromycin. However, <i>mocdc27</i> knock down mutants formed appressoria identical to those of the wild-type fungi. Therefore, it may also be likely that a complex of roxithromycin-MoCDC27 affects another molecule involved in appressorium formation. <i>mocdc27</i> encodes a protein that is highly homologous to the anaphase promoting complex/cyclosome(APC/C) subunit (CDC27/APC3) of other eukaryotes. CDC27 homologs have been detected in yeasts, plants, and mammals. CDC27 plays a key role in colorectal cancer as CDC27 expression is significantly correlated with tumor progression and poor patient survival [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 261" title="Qiu L, Wu J, Pan C, Tan X, Lin J, Liu R, Chen S, Geng R, Huang W. Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1. Cell Death Dis. 2016;7:e2074. 
 https://doi.org/10.1038/cddis.2015.402
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR261" id="ref-link-section-d32404569e1753">261</a>]. These findings and the interaction of macrolides with MoCDC27 may help to explain why macrolides exert anti-neoplastic effects (Table S1).</p><h3 class="c-article__sub-heading" id="Sec10">Chloramphenicol</h3><p>Chloramphenicol inhibits translation by binding with its nitrobenzyl ring to several nucleotides of the 23S rRNA at the A site of the peptidyl transferase centre. The aromatic ring of the ribosome-bound chloramphenicol overlaps with the A-site, so that the aminoacyl moiety of incoming aminoacyl-tRNA cannot properly attach to peptidyl transferase centre. Originally, inhibition of translation was thought to be universal. However, the inhibitory activity of chloramphenicol is context specific. Inhibition depends on the nature of specific amino acids in the nascent chain and the identity of the residue entering the A site [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Chloramphenicol PS. In: Corcoran JW, Hahn FE, Snell JF, Arora KL, editors. Antibitoics: mechanism of action of antimicrobial and antitumor agents. Berlin, Heidelberg, New York: Springer-Verlag; 1975. p. 370–95. " href="#ref-CR262" id="ref-link-section-d32404569e1765">262</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Dunkle JA, Xiong L, Mankin AS, Cate JH. Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action. Proc Nat Acad Sci. 2010;107:17152–7. 
 https://doi.org/10.1073/pnas.1007988107
 
 . " href="#ref-CR263" id="ref-link-section-d32404569e1765_1">263</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Bulkley D, Innis CA, Blaha G, Steitz TA. Revisiting the structures of several antibiotics bound to the bacterial ribosome. Proc Nat Acad Sci. 2010;107:17158–63. 
 https://doi.org/10.1073/pnas.1008685107
 
 . " href="#ref-CR264" id="ref-link-section-d32404569e1765_2">264</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 265" title="Tereshchenkov AG, Dobosz-Bartoszek M, Osterman IA, Marks J, Sergeeva VA, Kasatsky P, Komarova ES, Stavrianidi AN, Rodin IA, Kvega AL, Sergiev PV, Sumbatyan NV, Mankin AS, Bogdanov AA, Polikanov YS. Binding and action of amino acid analogs of chloramphenicol upon the bacterial ribosome. J Mol Biol. 2018;430:842–52. 
 https://doi.org/10.1016/j.jmb.2018.01.016
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR265" id="ref-link-section-d32404569e1768">265</a>]. Chloramphenicol readily binds to mitochondrial- but not to mammalian cytoplasmic ribosomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Barnhill AE, Brewer MT, Carlson SA. Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of host mitochondrial compnts. Antimicrob Agents Chemother. 2012;56:4046–51. 
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 . " href="#ref-CR268" id="ref-link-section-d32404569e1771_2">268</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Ibrahim NG, Burke JP, Beattie DS. The sensitivity of rat liver and yeast mitochondrial ribosomes to inhibitors of protein synthesis. J Biol Chem. 1974;249:6806–11 ((PMID: 4609092)). " href="#ref-CR269" id="ref-link-section-d32404569e1771_3">269</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 270" title="Lamb AJ, Clark-Walker GD, Linnane AW. The biogenesis of mitochondria 4 The differentiation of mitochondrial and cytoplasmic protein synthesizing systems in vitro by antibiotics. Biochim Biophys Acta. 1968;161:415–27. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR270" id="ref-link-section-d32404569e1774">270</a>]. Data summarized in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s15010-020-01536-y#Tab1">1</a> demonstrate that chloramphenicol affected read-through in eukaryotes, too [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 242" title="Thompson J, Pratt CA, Dahlberg AE. Effects of a number of classes of 50S inhibitors on stop codon readthrough during protein synthesis. Antimicrob Agents Chemother. 2004;48:4889–91. 
 https://doi.org/10.1128/AAC.48.12.4889-4891.2004
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR242" id="ref-link-section-d32404569e1781">242</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Thompson J, O’Connor M, Mills JA, Dahlberg AE. The protein synthesis inhibitors, oxazolidins and chloramphenicol, cause extensive translational inaccuracy in vivo. J Mol Biol. 2002;322:273–9. 
 https://doi.org/10.1016/S0022-2836(02)00784-2
 
 . " href="#ref-CR271" id="ref-link-section-d32404569e1784">271</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Tobe R, Naranjo-Suarez S, Everley RA. High error rates in selenocysteine insertion in mammalian cells treated with the antibiotic doxycycline, chloramphenicol, or geneticin. J Biol Chem. 2013;288:14700–15. 
 https://doi.org/10.1074/jbc.M112.446666
 
 . " href="#ref-CR272" id="ref-link-section-d32404569e1784_1">272</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Mayer FQ, Artigalas OA, Lagranha VL, Baldo G, Schwartz IV, Matte U, Giugliani R. Chloramphenicol enhances IDUA activity on fibroblasts from mucopolysaccharidosis I patients. Curr Pharm Biotechnol. 2013;14:194–8. 
 https://doi.org/10.2174/138920113805219467
 
 . " href="#ref-CR273" id="ref-link-section-d32404569e1784_2">273</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 274" title="Fan Y, Evans CR, Barber KW, Banerjee K, Weiss KJ, Margolin W, Igoshin OA, Rinehart J, Ling J. Heterogeneity of stop codon readthrough in single bacterial cells and implications for population fitness. Mol Cell. 2017;67:826–36. 
 https://doi.org/10.1016/j.molcel.2017.07.010
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR274" id="ref-link-section-d32404569e1787">274</a>]. The impact of chloramphenicol on gene expression in eukaryotes is possibly due to alternative mechanisms or downstream effects to inhibition of mitochondrial translation resulting in decreases in cell surface transferrin expression, de novo ferritin synthesis, thus affecting iron dependent respiratory chain activity resulting in an reduced ATP synthesis and eventually in reduced tumor cell growth (Table S1). It has been shown recently that chloramphenicol inhibited appressorium formation in <i>Magnaporthe oryzae</i> because of an inhibition of MoDullard, a serine/threonine phosphatase [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 275" title="Nozaka A, Nishiwaki A, Nagashima Y, Endo S, Kuroki M, Nakajima M, Narukawa M, Kamisuki S, Arazoe T, Taguchi H, Sugawara F, Kamakura T. Chloramphenicol inhibits eukaryotic Ser/Thr phosphatase and infection-specific cell differentiation in the rice blast fungus. Sci Rep. 2019;9:9283. 
 https://doi.org/10.1038/s41598-019-41039-x
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR275" id="ref-link-section-d32404569e1793">275</a>]. Alignment and comparison of amino acid sequences of fungal and human origin revealed that five MoDullard orthologs could be identified from the human genome but only caboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1 (CTDSP1) complemented the MoDullard function and could be inhibited by chloramphenicol. Small serine phosphatases can exhibit multiple functions in a variety of cellular and biological processes. Human CTDSP1 interacts with a variety of proteins like cell division cycle associated protein 3, myelin basic protein, RE1-silencing transcription factor, some of which are involved in cell differentiation [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 275" title="Nozaka A, Nishiwaki A, Nagashima Y, Endo S, Kuroki M, Nakajima M, Narukawa M, Kamisuki S, Arazoe T, Taguchi H, Sugawara F, Kamakura T. Chloramphenicol inhibits eukaryotic Ser/Thr phosphatase and infection-specific cell differentiation in the rice blast fungus. Sci Rep. 2019;9:9283. 
 https://doi.org/10.1038/s41598-019-41039-x
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR275" id="ref-link-section-d32404569e1796">275</a>]. If CTDSP1 may represent a novel target for chloramphenicol in humans has to be verified or falsified. It also has to be examined if interaction of chloramphenicol with CTDSP1 may have an impact on CTDSP1-networks with a variety of proteins being involved in cell differentiation and carcinogenesis. But anyway, an unexpected chloramphenicol target has been identified in humans.</p><h3 class="c-article__sub-heading" id="Sec11">Oxazolidinones</h3><p>Most of the studies on the mode of action of oxazolidinones have been performed with linezolid. Linezolid and earlier oxazolidinone derivatives were found to interfere with the early phase of protein synthesis, i.e. the formation of a functional 70S initiation complex with the two ribosomal subunits due to binding of linezolid to both subunits [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Slee AM, Wuonola MA, McRipley RJ, Zajac I, Zawada MJ, Bartholomew PT, Gregory WA, Forbes M. Oxazolidins, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721. Antimicrob Agents Chemother. 1987;31:1791–17970. 
 https://doi.org/10.1128/AAC.31.11.1791
 
 . " href="#ref-CR276" id="ref-link-section-d32404569e1807">276</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Daly JS, Eliopoulos GM, Reiszner E, Moellering RC Jr. Activity and mechanism of action of DuP 105 and DuP 721, new oxazolidin compounds. J Antimicrob Chemother. 1988;21:721–30. 
 https://doi.org/10.1093/jac/21.6.721
 
 . " href="#ref-CR277" id="ref-link-section-d32404569e1807_1">277</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Eustice DC, Feldman PA, Zajac I, Slee AM. Mechanism of action of DuP 721: inhibition of an early event during initiation of protein synthesis. Antimicrob Agents Chemother. 1988;32:1218–22. 
 https://doi.org/10.1128/aac.32.8.1218
 
 . " href="#ref-CR278" id="ref-link-section-d32404569e1807_2">278</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 279" title="Matassova NB, Rodnina MV, Endermann R, Kroll HP, Pleiss U, Wild H, Wintermeyer W. Ribosomal RNA is the target for oxazolidins, a novel class of translational inhibitors. RNA. 1999;5:939–46. 
 https://doi.org/10.1017/S1355838299990210
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR279" id="ref-link-section-d32404569e1810">279</a>]. However, biochemical- and target binding studies suggested that oxazolidinones not only interfere with the formation of the initiation complex but interfere with almost each and every step of protein synthesis like elongation factor G dependent translocation during elongation and frameshifting, termination of translation, and nonsense suppression [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 280" title="Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell SR, Fucini P. The oxazolidin antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc Nat Acad Sci. 2008;105:13339–44. 
 https://doi.org/10.1073/pnas.0804276105
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR280" id="ref-link-section-d32404569e1813">280</a>]. Also, resistance mutations mapping provided conflicting data. Docking studies and crystallography revealed that linezolid bound to the 50S ribosomal subunit in the A site pocket at the peptidyltransferase centre [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 280" title="Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell SR, Fucini P. The oxazolidin antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc Nat Acad Sci. 2008;105:13339–44. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR280" id="ref-link-section-d32404569e1816">280</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 281" title="Ippolito JA, Kanyo F, Wang D, Franceschi FJ, Moore PB, Steitz TA, Duffy EM. Crystal structure of the oxazolidin antibiotic linezolid bound to the 50S ribosomal subunit. J Med Chem. 2008;51:3353–6. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR281" id="ref-link-section-d32404569e1819">281</a>]. Binding to the A site impeded the proper placement of incoming aminoacyl-tRNAs and also binding of other protein synthesis inhibitors like chloramphenicol [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell SR, Fucini P. The oxazolidin antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc Nat Acad Sci. 2008;105:13339–44. 
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 . " href="#ref-CR280" id="ref-link-section-d32404569e1823">280</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Ippolito JA, Kanyo F, Wang D, Franceschi FJ, Moore PB, Steitz TA, Duffy EM. Crystal structure of the oxazolidin antibiotic linezolid bound to the 50S ribosomal subunit. J Med Chem. 2008;51:3353–6. 
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 . " href="#ref-CR281" id="ref-link-section-d32404569e1823_1">281</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 282" title="Lin AH, Murray RW, Vidmar TJ, Marotti KR. The oxazolidin eperezolid binds to the 50S ribosomal subunit and competes with binding of chloramphenicol and lincomycin. Antimicrob Agents Chemother. 1997;41:2127–31. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR282" id="ref-link-section-d32404569e1826">282</a>]. Linezolid inhibits peptide-bond formation not globally, but rather blocks translation at specific locations within the mRNA in a context-specific manner [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 283" title="Marks J, Kannan K, Roncase EJ, Klepacki D, Kefi A, Orelle C, Vázquez-Laslop N, Mankin AS. Context-specific inhibition of translation by ribosomal antibiotics targeting the peptidyl transferase center. Proc Nat Acad Sci. 2016;113:12150–5. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR283" id="ref-link-section-d32404569e1829">283</a>]. Linezolid binds exclusively to mitochondrial ribosomes and leaves cytoplasmic ribosomes unaffected [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 284" title="Saini JS, Homeyer N, Fulle S, Gohlke H. Determinants of the species selectivity of oxazolidin antibiotics targeting the large ribosomal subunit. Biol Chem. 2013;394:1529–41. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR284" id="ref-link-section-d32404569e1832">284</a>]. Linezolid and to a higher degree the investigational oxazolidinone R χ -01, increased frameshifting and stop codon read-through with nonsense suppression [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 271" title="Thompson J, O’Connor M, Mills JA, Dahlberg AE. The protein synthesis inhibitors, oxazolidins and chloramphenicol, cause extensive translational inaccuracy in vivo. J Mol Biol. 2002;322:273–9. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR271" id="ref-link-section-d32404569e1835">271</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 285" title="Skripkin E, McConnell TS, DeVito J, Lawrence L, Ippolito JA, Duffy EM, Sutcliffe J, Franceschi F. R chi-01, a new family of oxazolidins that overcome ribosome-based linezolid resistance. Antimicrob Agents Chemother. 2008;52:3550–7. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR285" id="ref-link-section-d32404569e1838">285</a>]. Consequently, linezolid and tedizolid caused mitochondrial dysfunction thus suppressing cancer cell growth and increasing apoptosis [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Zhu Y, Weldon JE. Evaluating the influence of common antibiotics on the efficacy of a recombinant immunotoxin in tissue culture. BMC Res Notes. 2019;12:293. 
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 . " href="#ref-CR286" id="ref-link-section-d32404569e1842">286</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Esner M, Graifer D, Lleonart ME, Lyakhovich A. Targeting cancer cells through antibiotics-induced mitochondrial dysfunction requires autophagy inhibition. Cancer Lett. 2017;384:60–9. 
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 . " href="#ref-CR287" id="ref-link-section-d32404569e1842_1">287</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Abad E, García-Mayea Y, Mir C, Sebastian D, Zorzano A, Potesil D, Zdrahal Z, Lyakhovich A, Lleonart ME. Common metabolic pathways implicated in resistance to chemotherapy point to a key mitochondrial role in breast cancer. Mol Cell Proteom. 2019;18:231–44. 
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 . " href="#ref-CR288" id="ref-link-section-d32404569e1842_2">288</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 289" title="Sharon D, Cathelin S, Mirali S, Di Trani JM, Yanofsky DJ, Keon KA, Rubinstein JL, Schimmer AD, Ketela T, Chan SM. Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response. Sci Transl Med 2019; 11(516). 
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 " href="/article/10.1007/s15010-020-01536-y#ref-CR289" id="ref-link-section-d32404569e1845">289</a>]. Linezolid also inhibited overexpression of mucin MUC5AC in human airway epithelial cells at concentrations of 5 and 20 mg/L due to inhibition of phosphorylation of ERK1/2, which caused the activation of a MAPK pathway member resulting in overexpression of MUC5AC. This effect is analogous to that seen with azithromycin, which reduced mucin production via the NF-κB pathway [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Kaku N, Yanagihara K, Morinaga Y, Yamada K, Harada Y, Migiyama Y, Nagaoka K, Nakamura S, Izumikawa K, Kohno S. Immunomodulatory effect of linezolid on methicillin-resistant Staphylococcus aureus supernatant-induced MUC5AC overexpression in human airway epithelial cells. Antimicrob Agents Chemother. 2014;58:4131–7. 
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 . " href="#ref-CR290" id="ref-link-section-d32404569e1848">290</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Wang J, Xia L, Wang R, Cai Y. Linezolid and its immunomodulatory effect: in vitro and in vivo evidence. Front Pharmacol. 2019;10:1389. 
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 . " href="#ref-CR291" id="ref-link-section-d32404569e1848_1">291</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 292" title="Yamada K, Morinaga Y, Yanagihara K, Kaku N, Harada Y, Uno N, Nakamura S, Imamura Y, Hasegawa H, Miyazaki T, Izumikawa K, Kakeya H, Mikamo H, Kohno S. Azithromycin inhibits MUC5AC induction via multidrug-resistant Acinetobacter baumannii in human airway epithelial cells. Pulm Pharmacol Ther. 2014;28:165–70. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR292" id="ref-link-section-d32404569e1851">292</a>].</p><h3 class="c-article__sub-heading" id="Sec12">Tetracyclines</h3><p>Tetracyclines inhibit bacterial protein synthesis by preventing the association of aminoacyl-tRNA with the bacterial ribosome. Tetracyclines bind to the 30S ribosomal subunit at high-occupancy tetracycline-binding site (Tet-1) and five other minor binding sites in 16S rRNA. Tetracycline most likely binds complexed with two Mg<sup>2+</sup> ions at the Tet-1 site near the A-site. A comparison of tigecycline- and tetracycline binding sites to the 70S ribosome and tigecycline binding to the 30S ribosome, respectively, showed that tigecycline was bound only to the Tet-1 site, and secondary binding sites were not observed. Thus, the significance of the other five tetracycline-binding sites is unclear [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 293" title="Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65:232–60. 
 https://doi.org/10.1128/MMBR.65.2.232-260.2001
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR293" id="ref-link-section-d32404569e1864">293</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 294" title="Grossman TH. Tetracycline antibiotics and resistance. CSH Perspect Med. 2016;6:a025387. 
 https://doi.org/10.1101/cshperspect.a025387
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR294" id="ref-link-section-d32404569e1867">294</a>]. In addition, tetracyclines bind to various synthetic double-stranded RNAs, suggesting that the double-stranded structures may play a more important role in binding of tetracyclines to RNA than binding to specific base pairs [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Chuckwudi C. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob Agents Chemother. 2016;60:4433–41. 
 https://doi.org/10.1128/AAC.00594-16
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR20" id="ref-link-section-d32404569e1870">20</a>]. This also implies that tetracyclines bind to double-stranded RNAs of pro- as well as eukaryotic origin. Furthermore, doxycycline bound to human cytosolic 80S ribosomes, so that human 80S ribosomal translation was modified and the cellular integrated stress response was activated [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 295" title="Mortison JD, Schen M, Myers JA, Zhang Z, Chen L, Ciarlo C, Comer E, Natchiar SK, Carr SA, Klaholz BP, Myers AG. Tetracyclines modify translation by targeting key human rRNA substructures. Cell Chem Biol. 2018;25:1506–18. 
 https://doi.org/10.1016/j.chembiol.2018.09.010
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR295" id="ref-link-section-d32404569e1873">295</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 296" title="Boer RE, Schneekloth JS Jr. Targeting mammalian translational inhibition with tetracyclines. Cell Chem Biol. 2018;25:1437–8. 
 https://doi.org/10.1016/j.chembiol.2018.12.006
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR296" id="ref-link-section-d32404569e1877">296</a>]. These findings contribute to an explanation why tetracyclines induced read-through of PTCs [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 272" title="Tobe R, Naranjo-Suarez S, Everley RA. High error rates in selenocysteine insertion in mammalian cells treated with the antibiotic doxycycline, chloramphenicol, or geneticin. J Biol Chem. 2013;288:14700–15. 
 https://doi.org/10.1074/jbc.M112.446666
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR272" id="ref-link-section-d32404569e1880">272</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 273" title="Mayer FQ, Artigalas OA, Lagranha VL, Baldo G, Schwartz IV, Matte U, Giugliani R. Chloramphenicol enhances IDUA activity on fibroblasts from mucopolysaccharidosis I patients. Curr Pharm Biotechnol. 2013;14:194–8. 
 https://doi.org/10.2174/138920113805219467
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR273" id="ref-link-section-d32404569e1883">273</a>] and exerted anti-proliferative effects on human cancer cell lines and in patients (Table S1). Favourable clinical outcomes have also been observed with tetracyclines in indications like rheumatoid arthritis, osteoarthritis, Fragile X syndrome, etc. [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 129" title="Lindeman JH, Abdul-Hussien H, van Bockel JH, Wolterbeek R, Kleemann R. Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm. Doxycycline selectively depletes aortic wall neutrophils and cytotoxic T cells. Circulation. 2009;119:2209–16. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR129" id="ref-link-section-d32404569e1886">129</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 131" title="Hackmann AE, Rubin BG, Sanchez LA, Geraghty PA, Thompson RW, Curci JA. A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair. J Vasc Surg. 2008;48:519–26. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR131" id="ref-link-section-d32404569e1889">131</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="O’Dell JR, Elliott JR, Mallek JA, Mikuls TR, Weaver CA, Glickstein S, Blakely KM, Hausch R, Leff RD. Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus methotrexate al. Arthritis Rheum. 2006;54:621–7. 
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 . " href="#ref-CR297" id="ref-link-section-d32404569e1892">297</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Brandt KD, Mazzuca SA, Katz BP, Lane KA, Buckwalter KA, Yocum DE, Wolfe F, Schnitzer TJ, Moreland LW, Manzi S, Sharma L, Oddis CV, Hugenberg ST, Heck LW. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. 2005;52:2015–25. 
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 . " href="#ref-CR298" id="ref-link-section-d32404569e1892_1">298</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Walker C, Puumala S, Golub LM, Str JA, Reinhardt RA, Lee HM, Payne JB. Subantimicrobial dose doxycycline effects on osteopenic b loss: microbiologic results. J Periodontol. 2007;78:1590–601. 
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 . " href="#ref-CR299" id="ref-link-section-d32404569e1892_2">299</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Leigh MJ, Nguyen DV, Mu Y, Winarni TI, Schneider A, Chechi T, Polussa J, Doucet P, Tass F, Rivera SM, Hesse D, Hagerman RL. A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome. J Dev Behav Pediatr. 2013;34:147–55. 
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 . " href="#ref-CR300" id="ref-link-section-d32404569e1892_3">300</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Dodd BR, Spence RA. Doxycycline inhibition of abdominal aortic aneurysm growth—a systematic review of the literature. Curr Vasc Pharmacol. 2011;9:471–8. 
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 . " href="#ref-CR301" id="ref-link-section-d32404569e1892_4">301</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Abdul-Hussien H, Hanemaaijer R, Verheijen JH, van Bockel JH, Geelkerken RH, Lindeman JH. Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content. J Vasc Surg. 2009;49:741–9. 
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 . " href="#ref-CR302" id="ref-link-section-d32404569e1892_5">302</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Baxter BT, Matsumura J, Curci JA, McBride R, Larson LA, Blackwelder W, Lam D, Wijesinha M, Terrin M. Effect of doxycycline on aneurysm growth among patients with small infrarenal abdominal aortic aneurysms: a randomized clinical trial. JAMA. 2020;323:2019–38. 
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 . " href="#ref-CR303" id="ref-link-section-d32404569e1892_6">303</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 304" title="Meijer CA, Stijnen T, Wasser MN, Hamming JF, van Bockel JH, Lindeman JH. Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial. Ann Intern Med. 2013;159:815–23. 
 https://doi.org/10.7326/0003-4819-159-12-201312170-00007
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR304" id="ref-link-section-d32404569e1896">304</a>]. A comprehensive summary of pleiotropic non-antibacterial actions and on-going clinical trials was published in 2010 [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 11" title="Griffin MO, Fricovsky E, Ceballos G, Villarreal F. Tetracyclines: a pleiotropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010a;299:C539–48. 
 https://doi.org/10.1152/ajpcell.00047.2010
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR11" id="ref-link-section-d32404569e1899">11</a>] listing 54 and 88 clinical trials for minocycline and doxycycline, respectively, in indications like e.g. asthma, autism, Parkinson’s disease, amyothrophic lateral sclerosis.</p><p>Tetracyclines also exhibit an anti-parasitic effect and affect growth of e.g.</p><p><i>Plasmodium falciparum, Entamoeba histolytica, Giardia lamblia, Leishmania major, Trichomonas vaginalis,</i> and <i>Toxoplasma gondii</i> [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Chuckwudi C. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob Agents Chemother. 2016;60:4433–41. 
 https://doi.org/10.1128/AAC.00594-16
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR20" id="ref-link-section-d32404569e1913">20</a>]. The antiparasitic activity is explained by protein synthesis inhibition in mitochondria. However, <i>T. vaginalis, G. lamblia,</i> and <i>E. histolytica</i> are devoid of mitochondria but are nevertheless susceptible to tetracyclines. Thus, tetracyclines should affect structures in eukaryotes other than just mitochondria. Five not necessarily mutually exclusive theories are discussed: First, tetracyclines may inhibit translation in bacterial endosymbionts, like Wolbachia in helminths, being essential for parasite survival and reproduction [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Chuckwudi C. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob Agents Chemother. 2016;60:4433–41. 
 https://doi.org/10.1128/AAC.00594-16
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR20" id="ref-link-section-d32404569e1922">20</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 305" title="Sironi M, Bandi C, Sacchi L, Di Sacco B, Damiani G, Genchi C. Molecular evidence for a close relative of the arthropod endosymbiont Wolbachia in a filarial worm. Mol Biochem Parasitol. 1995;74:223–7. 
 https://doi.org/10.1016/0166-6851(95)02494-8
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR305" id="ref-link-section-d32404569e1926">305</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 306" title="Rao RU, Huang Y, Abubucker S, Heinz M, Crosby SD, Mitreva M, Weil GJ. Effects of Doxycycline on gene expression in Wolbachia and Brugia malayi adult female worms in vivo. J Biomed Sci. 2012;19:21. 
 https://doi.org/10.1186/1423-0127-19-21
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR306" id="ref-link-section-d32404569e1929">306</a>]. Second, eukaryotes without mitochondria may contain mitochondria derived organelles like mitosomes and hydrogenosomes [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 307" title="Dolezal P, Smíd O, Rada P, Zubácová Z, Bursać D, Suták R, Nebesárová J, Lithgow T, Tachezy J. Giardia mitosomes and trichomonad hydrogenosomes share a common mode of protein targeting. Proc Nat Acad Sci. 2005;102:10924–9. 
 https://doi.org/10.1073/pnas.0500349102
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR307" id="ref-link-section-d32404569e1932">307</a>], so that such organisms contain genes of mitochondrial ancestry. Tetracycline targeted the hydrogenosome of <i>T. vaginalis</i> thus causing cell death [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 308" title="Huang KY, Ku FM, Cheng WH, Lee CC, Huang PJ, Chu LJ, Fang YK, Wu HH, Tang P. Novel insights into the molecular events linking to cell death induced by tetracycline in the amitochondriate protozoan Trichomonas vaginalis. Antimicrob Agents Chemother. 2015;59:6891–903. 
 https://doi.org/10.1128/AAC.01779-15
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR308" id="ref-link-section-d32404569e1938">308</a>]. <i>P. falciparum</i> harbours a plastid (apicoplast) that originated from an eukaryotic algal lineage. This organelle, too, is inhibited by tetracycline [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 309" title="Lin Q, Katakura K, Suzuki M. Inhibition of mitochondrial and plastid activity of Plasmodium falciparum by minocycline. FEBS Lett. 2002;515:71–4. 
 https://doi.org/10.1016/S0014-5793(02)02437-7
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR309" id="ref-link-section-d32404569e1945">309</a>]. Third, binding of the tetracyclines to double stranded RNA may represent an alternative to the ribosomal target site thus allowing tetracyclines to affect organisms that lack the 16S ribosomal RNA (such as RNA-viruses and some protozoa) [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Chuckwudi C. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob Agents Chemother. 2016;60:4433–41. 
 https://doi.org/10.1128/AAC.00594-16
 
 . " href="/article/10.1007/s15010-020-01536-y#ref-CR20" id="ref-link-section-d32404569e1948">20</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 310" title="Chukwudi CU, Good L. Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action. J Antibiot. 2016;69:622–30. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR310" id="ref-link-section-d32404569e1951">310</a>]. Fourth, tetracyclines are strong chelators of divalent cations other than zinc [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Lambs L, Venturini M, Decock-Le Reverend B, Kozlowski H, Berthon G. Metal ion-tetracycline interactions in biological fluids. Part 8. Potentiometric and spectroscopic studies on the formation of Ca(II) and Mg(II) complexes with 4-dedimethylamino-tetracycline and 6-desoxy-6-demethyl-tetracycline. J Inorg Biochem. 1988;33:193–210. 
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 . " href="#ref-CR311" id="ref-link-section-d32404569e1954">311</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Grenier D, Huot MP, Mayrand D. Iron-chelating activity of tetracyclines and its impact on the susceptibility of Actinobacillus actinomycetemcomitans to these antibiotics. Antimicrob Agents Chemother. 2000;44:763–6. 
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 . " href="#ref-CR312" id="ref-link-section-d32404569e1954_1">312</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Caswell AH, Hutchison JD. Selectivity of cation chelation to tetracyclines: evidence for special conformation of calcium chelate. Biochem Biophysical Res Commun. 1971;43:625–30. 
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 . " href="#ref-CR313" id="ref-link-section-d32404569e1954_2">313</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 314" title="Brion M, Lambs L, Berthon G. Metal ion-tetracycline interactions in biological fluids. Part 5. Formation of zinc complexes with tetracycline and some of its derivatives and assessment of their biological significance. Agents Actions. 1985;17:229–42. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR314" id="ref-link-section-d32404569e1957">314</a>], so that tetracyclines interact not only with metallo matrixproteinases (see paragraph 2.2. and Tables S1, S2), but affected also the interaction with double stranded RNA and thus their own uptake into Gram-negative bacteria, and their affinities to pro- or eukaryotic targets [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Chuckwudi C. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob Agents Chemother. 2016;60:4433–41. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR20" id="ref-link-section-d32404569e1960">20</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 294" title="Grossman TH. Tetracycline antibiotics and resistance. CSH Perspect Med. 2016;6:a025387. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR294" id="ref-link-section-d32404569e1964">294</a>]. Fifth, tetracyclines acted as pro-apoptotics in various cell-lines [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 11" title="Griffin MO, Fricovsky E, Ceballos G, Villarreal F. Tetracyclines: a pleiotropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010a;299:C539–48. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR11" id="ref-link-section-d32404569e1967">11</a>, <a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 20" title="Chuckwudi C. rRNA binding sites and the molecular mechanism of action of the tetracyclines. Antimicrob Agents Chemother. 2016;60:4433–41. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR370" id="ref-link-section-d32404569e2096">370</a>]. RNA helicases have been implicated in proofreading processes. of these helicases, i.e. DHX9 has a key function in the regulation of biological processes, including tumorigenesis. Enoxacin inhibited DHX9 which is found in patients with lung- and prostate cancers [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 371" title="Jankowsky E. RNA helicases at work: binding and rearranging. Trends Biochem Sci. 2011;36:19–29. 
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 . " href="/article/10.1007/s15010-020-01536-y#ref-CR389" id="ref-link-section-d32404569e2132">389</a>]. Thus, patients with parasitic infections may benefit from fluoroquinolone treatment twofold: they are going to be treated not only of bacterial- but also of opportunistic parasitic infections, so that fluoroquinolone therapy should probably not be withdrawn upon elimination or exclusion of the bacterial pathogen.</p></div></div></section><section data-title="Conclusions and open questions"><div class="c-article-section" id="Sec14-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec14">Conclusions and open questions</h2><div class="c-article-section__content" id="Sec14-content"><p>A synopsis of non-antimicrobial activities of antibiotics is provided in Table <a data-track="click" data-track-label="link" data-track-action="table anchor" href="/article/10.1007/s15010-020-01536-y#Tab2">2</a>. In general, antibiotics interacted with multiple targets and exerted pleiotropic effects in eukaryotes. Many of these targets are multi-functional, so that one specific effect cannot be attributed to one specific target and agent. In addition, different drug classes caused identical effects in eukaryotes. Thus, the anyhow complex modes of actions of antibiotics in eukaryotes may be even more multifaceted.</p><div class="c-article-table" data-test="inline-table" data-container-section="table" id="table-2"><figure><figcaption class="c-article-table__figcaption"><b id="Tab2" data-test="table-caption">Table 2 Synopsis of non-antibacterial activities and modes of action of antibiotics in eukaryotes</b></figcaption><div class="u-text-right u-hide-print"><a class="c-article__pill-button" data-test="table-link" data-track="click" data-track-action="view table" data-track-label="button" rel="nofollow" href="/article/10.1007/s15010-020-01536-y/tables/2" aria-label="Full size table 2"><span>Full size table</span><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-right-small"></use></svg></a></div></figure></div><p>It is important to emphasize that the majority of studies reviewed above were planned as hypothesis generating preclinical experiments or retrospective observational clinical studies rather than prospective, randomized clinical trials, so that evidence supporting these potential novel indications varies widely. But still these data demonstrate that antibiotics interact with eukaryotic targets, so that therapeutic options of an antibiotic treatment may likely be more diverse than expected. Although none of the antibiotics should be used at the time being for monotherapy of non-infectious diseases, they could be used as adjunctive therapeutics in cancer patients or patients with parasitic diseases. Macrolides, tetracyclines, aminoglycosides, and fluoroquinolones have been shown to be clinically effective as anti-neoplastic agents, even in monotherapy, and were found to synergise with cancer drugs. Therefore, antibiotics could possibly be used not only for prophylaxis- or treatment of bacterial infections, but also for adjuvant therapy in cancer patients. Treatment modalities could hypothetically be individualized by selecting agents for prophylaxis or treatment of bacterial infections which are active against the specific cancer type and which synergize with the specific cancer drug administered to the patient. Likewise, tetracyclines and fluoroquinolones exerting anti-parasitic activities should probably not be withdrawn upon elimination or exclusion of the bacterial pathogen but should be continued in parallel to administration of the specific anti-parasitic agent. Their activities against RNA-viruses [<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" title="Dalhoff A. Antiviral, antifungal, and antiparasitic activities of fluoroquinols optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action? Eur J Clin Microbiol Infect Dis. 2015;34:661–8. 
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A purposeful use of antibiotics not only as antibacterial agents but also as agents targeting the human body and his functions should be considered.</p></div></div></section><section data-title="Addendum search strategy"><div class="c-article-section" id="Sec15-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec15">Addendum search strategy</h2><div class="c-article-section__content" id="Sec15-content"><p>Publications addressing four topics were screened: first, impact of antibiotics on growth of eukaryotic/mammalian cells/cell cultures. Second, impact of antibiotics on mitochondrial functions, eukaryotic translation/transcription, and/or enzyme activities like metallo-matrix-proteinases, serine proteases, etc., read-through, premature stop codons. Third, interaction with mitosomes, 80S ribosome, RNA, DNA. Fourth, interaction of antibiotics with eukaryotic targets. Search strategy and selection criteria were based on the combination of key words sulphonamides, ß-lactams, aminoglycosides, macrolides, chloramphenicol, oxazolidinones, tetracyclines, fluoroquinolones, the corresponding single agents of these drug-classes, and antibiotics in general. Growth inhibition, tumor growth, inhibitory concentration IC<sub>50</sub>, homologous, orthologs, paralogs, chelation, complexation. 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Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?. <i>Infection</i> <b>49</b>, 29–56 (2021). https://doi.org/10.1007/s15010-020-01536-y</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1007/s15010-020-01536-y?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Received<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time 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