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class="site-main" id="main"> <article id="post-82" class="post-82 post type-post status-publish format-standard has-post-thumbnail hentry category-apicoplast tag-antimalarial-therapy tag-apicoplast tag-drug-target tag-evolutionary-biology tag-fatty-acid-synthesis tag-isoprenoid-biosynthesis tag-malaria tag-metabolic-pathways tag-plasmodium-falciparum tag-protein-targeting" itemtype="https://schema.org/CreativeWork" itemscope> <div class="inside-article"> <div class="featured-image page-header-image-single "> <img width="2560" height="1340" src="https://infect.blog/archive/wp-content/uploads/2024/09/image-36-min-scaled.jpg" class="attachment-full size-full" alt="" itemprop="image" decoding="async" fetchpriority="high" srcset="https://infect.blog/archive/wp-content/uploads/2024/09/image-36-min-scaled.jpg 2560w, https://infect.blog/archive/wp-content/uploads/2024/09/image-36-min-300x157.jpg 300w, https://infect.blog/archive/wp-content/uploads/2024/09/image-36-min-1024x536.jpg 1024w, https://infect.blog/archive/wp-content/uploads/2024/09/image-36-min-768x402.jpg 768w, https://infect.blog/archive/wp-content/uploads/2024/09/image-36-min-1536x804.jpg 1536w, https://infect.blog/archive/wp-content/uploads/2024/09/image-36-min-2048x1072.jpg 2048w" sizes="(max-width: 2560px) 100vw, 2560px" /> </div> <header class="entry-header"> <h1 class="entry-title" itemprop="headline">The Role of Apicoplasts in Malaria Parasites</h1> <div class="entry-meta"> <span class="posted-on"><time class="updated" datetime="2024-09-10T19:35:57+05:30" itemprop="dateModified">September 10, 2024</time><time class="entry-date published" datetime="2024-09-10T15:02:48+05:30" itemprop="datePublished">September 10, 2024</time></span> <span class="byline">by <span class="author vcard" itemprop="author" itemtype="https://schema.org/Person" itemscope><a class="url fn n" href="https://infect.blog/archive/author/infect/" title="View all posts by infect" rel="author" itemprop="url"><span class="author-name" itemprop="name">infect</span></a></span></span> </div> </header> <div class="entry-content" itemprop="text"> <p><span style="font-weight: 400;">Hundreds of millions of people all over the world suffer from malaria; hence, the millennium struggle to get it under control has pushed researchers to explore a multitude of scientific avenues to try and find any exploitable flaws in the malaria parasite, Plasmodium falciparum. One of the discoveries made is the apicoplast, which is a chloroplast found within this and other apicomplexan parasites. This organelle, a remnant of the photosynthetic ancestor of the parasite, has recently attracted great interest because of its unusual biological pathways and as a potential drug target. Together with its unique origin and metabolic functions, the fact that the apicoplast plays a crucial role in the life cycle of the parasite offers promising avenues for the development of new antimalarial therapies. The article below sheds some light on the multifaceted roles of the apicoplast, why it is an important factor, and its potential in the ongoing battle to squash malaria.</span></p> <h3><b>History and Structure of Apicoplast</b></h3> <p><span style="font-weight: 400;">The apicoplast seems to be an organelle essentially required in Plasmodium falciparum, and its evolutionary history is intriguing. Probably one of the most complex events to have occurred would be that of a secondary endosymbiosis event involving an ancestral eukaryote engulfing a red alga itself, already containing a primary chloroplast from a cyanobacterium. This organelle has lost its photosynthetic capability over time but has retained other vital functions necessary for survival.</span></p> <p><span style="font-weight: 400;">The apicoplast is bound by four membranes, an ultra-structural feature that reflects its colorful evolutionary history. The outer two of these membranes are derived from the host membranes of the endomembrane system, while the inner two represent various algal and cyanobacteria membranes. This structure has implications for its function and for the targeting of proteins synthesized in the cytosol and transported into the apicoplast</span><b>.</b></p> <h3><b>Functions of the Apicoplast</b></h3> <p><span style="font-weight: 400;">The apicoplast performs various critical activities within the malaria parasite’s biology. Therefore, key activities are metabolic pathways absent in the human host, making it an attractive target for antimalarial drugs. One of the most critical functions of apicoplasts is fatty acid synthesis. The apicoplast contains enzymes involved in the type II fatty acid synthesis pathway. The latter is different from the type I fatty acid synthase found in humans. This pathway is required for the synthesis of fatty acids involved in membrane biogenesis and parasite replication. Thus, inhibition of the enzymes in the FASII pathway will disrupt the life cycle of the parasite; therefore, such enzymes could become prime targets for drug development against this infection.</span></p> <p><span style="font-weight: 400;">Another critical pathway in the apicoplast is the non-mevalonate pathway of isoprenoid biosynthesis. This pathway produces the isoprenoids, which are dysfunctional molecules involved in electron transport, cell membrane maintenance, and protein prenylation. The fact that this pathway does not exist in humans brings the apicoplast forward as a selective drug target.</span></p> <p><b>Heme and Iron-Sulfur Cluster Biosynthesis</b><span style="font-weight: 400;">: The apicoplast also participates in the biosynthesis of heme and iron-sulfur clusters, two important cofactors in hundreds of different enzymatic reactions. Apicoplast synthesis of heme complements the heme derived from the host erythrocytes to provide adequate amounts to meet the metabolic demands of the parasite. Iron-sulfur clusters play a crucial role in electron transfer reactions and other metabolic processes.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Yearwise Publication Trend on <b>“<a href="https://infect.blog/publication-trends/index/apicoplast" target="_blank" title="apicoplast - yearwise publication trends">apicoplast</a>”</b></h2> </div> </div><div class="results-container"><div class="chart-block" style="padding:15px;"> <div class="left"> <div id="results" class="results"></div> </div> <div class="right"> <div class="chart-container"><canvas id="publicationChart"></canvas></div> </div> <div class="keywordsdiv"> <div style="text-align:center;"><b>Find publication trends on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-stats"></span> </div> </div></div></div><div class="inside-article"><style> table { margin: 0 0 1.5em; 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if (!statistics || Object.keys(statistics).length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var tableHTML = `<div class='pub-scroll'> <table class='tablediv' border='1' cellspacing='0' cellpadding='0'> <tr> <th>Year</th> <th>Publication Count</th> </tr>`; Object.entries(statistics).sort(([yearA], [yearB]) => yearB - yearA).forEach(([year, count]) => { const displayCount = count === 0 ? 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Targeting the organelle is mediated by leader sequences at the N-terminus of precursor proteins consisting of a signal peptide and a transit peptide. A signal peptide targets the protein into the secretory pathway and, after processing, the peptide into the apicoplast.</span></p> <p><span style="font-weight: 400;">This rather complicated mechanism of targeting probably occurs due to several successive steps: the recognition and translocation of the precursor protein with the help of a signal recognition particle into the endoplasmic reticulum; processing and transport—the signal peptide gets cleaved off, and the protein is transported via the secretory pathway to the apicoplast; import and maturation—the transit peptide gets cleaved upon entering the apicoplast, and the mature protein becomes functional within the organelle. Understanding and disrupting this process of targeting can open up new avenues for antimalarial drug development</span><b>.</b></p> <h3><b>Drug Target Potential of the Apicoplast</b></h3> <p><span style="font-weight: 400;">Metabolic pathways unique to the apicoplast, along with its essential functions, make it an attractive target for antimalarial drugs. Several classes of compounds have been identified that specifically target apicoplast functions, thus disrupting the lifecycle of the parasite without affecting the host.</span></p> <p><b>Antibiotics</b><span style="font-weight: 400;">: The action of most of the antibiotics, such as doxycycline and clindamycin, is focused on the prokaryote-like ribosomes of the apicoplast, where they act as protein synthesis inhibitors. Each of these antibiotics acts slowly but kills the parasites, which proves that the apicoplast has a crucial role in the survival of the parasite.</span></p> <p><b>Fosmidomycin and FR-900098</b><span style="font-weight: 400;">: These two drugs act by inhibiting the enzyme DOXP reductoisomerase, responsible for catalyzing the first step of the non-mevalonate pathway of isoprenoid biosynthesis. By targeting this pathway, these drugs effectively disrupt the production of essential isoprenoids.</span></p> <p><b>Triclosan and Thiolactomycin</b><span style="font-weight: 400;">: Triclosan inhibits the enoyl-acyl carrier protein reductase enzyme in the FASII pathway, whereas thiolactomycin acts as an inhibitor of beta-ketoacyl-ACP synthase. These two drugs work by crippling fatty acid synthesis, consequently killing the parasite.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Recent Publications on <b>“<a href="https://infect.blog/recent-publications/index/apicoplast" target="_blank" rel="noopener" title="apicoplast - yearwise publication list">apicoplast</a>”</b></h2> </div> </div> <div class="pb-main"><div class="article-scroll"><div id="results_recent" class="results"></div></div><div class="keywordsdiv" style="margin: 0px 15px;margin-top:20px;"> <div style="text-align:center;"><b>Find publications on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-papers"></span> </div></div></div><div class="inside-article"> <style> .pb-main{ border: solid 1px #ccc; border-top: none; margin-bottom: 20px; padding-bottom: 25px; background:#fff; } .author-main { border: solid 1px #ccc; border-top: none; margin-bottom: 20px; padding-bottom: 25px; background:#fff; } .publication-block { padding: 10px; margin-bottom: 10px; background-color: #f9f9f9; text-align: left; background: #FFF; border-bottom: solid 1px #ccc; margin-left: 15px; margin-right: 15px; } .publication-block h3 { margin: 0 0 10px; color: #000!important; } .publication-block a { font-size: 16px !important; line-height: 1em; font-weight: 600; text-transform: none; color: #000; padding: 0px; } .publication-block a:hover{ color: #227cdc; text-decoration:underline; } .article-scroll { max-height: 445px; overflow-y: auto; overflow-x: hidden; } ::-webkit-scrollbar-track { -webkit-box-shadow: inset 0 0 6px rgba(0,0,0,0.3); background-color: #efefef; border-radius:30px; } ::-webkit-scrollbar { width: 6px; background-color: #efefef; border-radius:30px; } ::-webkit-scrollbar-thumb { background-color: #ababab; 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publicationBlock.innerHTML = publicationHTML; resultsContainer.appendChild(publicationBlock); }); } function displayKeywordPapers(keywords) { var resultsContainer = document.getElementById('keyword-papers'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach((key, index) => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://infect.blog/recent-publications/index/${key_replace}" target="_blank" title="${key} - publication list">${key}</a>`; if (index < keywords.length - 1) { keywordHTML += ', '; } }); resultsContainer.innerHTML = keywordHTML; } // Call the function with the PHP data var recent_papers = [ { "title": "A pyruvate transporter in the apicoplast of apicomplexan parasites.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38865262", "publishedDate": "2024" }, { "title": "Protists: Eukaryotic single-celled organisms and the functioning of their organelles.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38821633", "publishedDate": "2024" }, { "title": "Drug Repurposing in the Chemotherapy of Infectious Diseases.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38338378", "publishedDate": "2024" }, { "title": "Detailing organelle division and segregation in .", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38352445", "publishedDate": "2024" }, { "title": "Identification of and Species in Muscles of Gray Wolf () from Lithuania.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38393103", "publishedDate": "2024" }, { "title": "CRISPR screens identify genes essential for virulence among proteins of hyperLOPIT-unassigned subcellular localization in .", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39082802", "publishedDate": "2024" }, { "title": "Apicoplast-derived isoprenoids are essential for biosynthesis of GPI protein anchors, and consequently for egress and invasion in Plasmodium falciparum.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39241090", "publishedDate": "2024" }, { "title": "The dynamin-related protein Dyn2 is essential for both apicoplast and mitochondrial fission in .", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38559241", "publishedDate": "2024" }, { "title": "Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A \\\\\\\"One-Health\\\\\\\" Concern.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38255695", "publishedDate": "2024" }, { "title": "Myosin F controls actin organization and dynamics in .", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38416592", "publishedDate": "2024" }, { "title": "Progressive heterogeneity of enlarged and irregularly shaped apicoplasts in persister blood stages after drug treatment.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38410435", "publishedDate": "2024" }, { "title": "Multiomics analysis reveals MO1 as a distinct species and provides insights into its evolution and virulence.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38293033", "publishedDate": "2024" }, { "title": "Putative molecular markers of resistance to antimalarial drugs in malaria parasites from Ghana.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38456076", "publishedDate": "2024" }, { "title": "The monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38502570", "publishedDate": "2024" }, { "title": "Hepatozoon (Eucoccidiorida: Hepatozoidae) in wild mammals of the Americas: a systematic review.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38444020", "publishedDate": "2024" }, { "title": "Potent hydroxamate-derived compounds arrest endodyogeny of Toxoplasma gondii tachyzoites.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38431113", "publishedDate": "2024" }, { "title": "Inhibitors against DNA Polymerase I Family of Enzymes: Novel Targets and Opportunities.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38666816", "publishedDate": "2024" }, { "title": "Gapless assembly of NVSL348.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38651914", "publishedDate": "2024" }, { "title": "A new and widespread group of fish apicomplexan parasites.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38821048", "publishedDate": "2024" }, { "title": "Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Parasites.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38765186", "publishedDate": "2024" } ]; var keywordsArray = ["Apicoplast","Malaria","Plasmodium falciparum","Fatty acid synthesis","Isoprenoid biosynthesis","Drug target","Antimalarial therapy","Protein targeting","Evolutionary biology","Metabolic pathways"]; displayResults_recent(recent_papers); displayKeywordPapers(keywordsArray); // function stripslashes(str) { // if (typeof str === 'string') { // return str.replace(/\/g, ''); // } // } </script></p> <h3><b>Conclusion</b></h3> <p><span style="font-weight: 400;">The apicoplast is a pillar in Plasmodium falciparum biology; it hosts a variety of activities that are essential for the survival of the parasite but are absent in humans. Its unusual origins and the presence of unique metabolic pathways make it an ideal target for novel antimalarial therapies. It is possible to exploit these differences in designing drugs that are potent yet selective, targeting the apicoplast to minimize damage to the host. With rising resistance to the current antimalarial arsenal, the apicoplast offers a promising new frontier in efforts to eliminate malaria.</span></p> <p></p> <h3><b>References</b></h3> <ol> <li> <div class="citation-text">Ralph SA, D’Ombrain MC, McFadden GI. <a href="https://pubmed.ncbi.nlm.nih.gov/11768328/">The apicoplast as an antimalarial drug target.</a> Drug Resist Updat. 2001 Jun;4(3):145-51. doi: 10.1054/drup.2001.0205. PMID: 11768328.</div> </li> <li>He, C.Y., Striepen, B., Pletcher, C.H., Murray, J.M. and Roos, D.S., 2001. <a href="https://www.jbc.org/article/S0021-9258(19)31656-4/fulltext">Targeting and processing of nuclear-encoded apicoplast proteins in plastid segregation mutants of Toxoplasma gondii</a>. <i>Journal of Biological Chemistry</i>, <i>276</i>(30), pp.28436-28442.</li> <li> <div class="citation-text">Waller RF, Keeling PJ, Donald RG, Striepen B, Handman E, Lang-Unnasch N, Cowman AF, Besra GS, Roos DS, McFadden GI. <a href="https://pubmed.ncbi.nlm.nih.gov/9770490/">Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum.</a> Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12352-7. doi: 10.1073/pnas.95.21.12352. PMID: 9770490; PMCID: PMC22835.</div> </li> <li> <div class="citation-text">Adams KL, Daley DO, Whelan J, Palmer JD. <a href="https://pubmed.ncbi.nlm.nih.gov/11971146/">Genes for two mitochondrial ribosomal proteins in flowering plants are derived from their chloroplast or cytosolic counterparts.</a> Plant Cell. 2002 Apr;14(4):931-43. doi: 10.1105/tpc.010483. PMID: 11971146; PMCID: PMC150693.</div> </li> <li> <div class="citation-text">Kemp LE, Bond CS, Hunter WN. <a href="https://pubmed.ncbi.nlm.nih.gov/11997478/">Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development.</a> Proc Natl Acad Sci U S A. 2002 May 14;99(10):6591-6. doi: 10.1073/pnas.102679799. Epub 2002 May 7. PMID: 11997478; PMCID: PMC124447.</div> </li> <li> <div class="citation-text">Roberts CW, Roberts F, Lyons RE, Kirisits MJ, Mui EJ, Finnerty J, Johnson JJ, Ferguson DJ, Coggins JR, Krell T, Coombs GH, Milhous WK, Kyle DE, Tzipori S, Barnwell J, Dame JB, Carlton J, McLeod R. <a href="https://pubmed.ncbi.nlm.nih.gov/11865437/">The shikimate pathway and its branches in apicomplexan parasites.</a> J Infect Dis. 2002 Feb 15;185 Suppl 1:S25-36. doi: 10.1086/338004. PMID: 11865437.</div> </li> <li> <div class="citation-text">Tan TH, Pach R, Crausaz A, Ivens A, Schneider A. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC133840/">tRNAs in Trypanosoma brucei: genomic organization, expression, and mitochondrial import.</a> Mol Cell Biol. 2002 Jun;22(11):3707-17. doi: 10.1128/MCB.22.11.3707-3716.2002. PMID: 11997507; PMCID: PMC133840.</div> </li> <li> <div class="citation-text">Rowe JA, Kyes SA, Rogerson SJ, Babiker HA, Raza A. <a href="https://pubmed.ncbi.nlm.nih.gov/11930336/">Identification of a conserved Plasmodium falciparum var gene implicated in malaria in pregnancy.</a> J Infect Dis. 2002 Apr 15;185(8):1207-11. doi: 10.1086/339684. Epub 2002 Apr 1. PMID: 11930336.</div> </li> </ol> </div> <footer class="entry-meta" aria-label="Entry meta"> <span class="cat-links"><span class="gp-icon icon-categories"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M0 112c0-26.51 21.49-48 48-48h110.014a48 48 0 0143.592 27.907l12.349 26.791A16 16 0 00228.486 128H464c26.51 0 48 21.49 48 48v224c0 26.51-21.49 48-48 48H48c-26.51 0-48-21.49-48-48V112z" /></svg></span><span class="screen-reader-text">Categories </span><a href="https://infect.blog/archive/category/apicoplast/" rel="category tag">Apicoplast</a></span> <span class="tags-links"><span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 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