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The Role of the Mycobacterial Cell Wall in Disease Pathogenesis – Infectious Diseases

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class="site-main" id="main"> <article id="post-113" class="post-113 post type-post status-publish format-standard has-post-thumbnail hentry category-pathogenesis tag-biosynthesis tag-cell-wall tag-drug-resistance tag-immune-evasion tag-lam tag-mycobacterium-tuberculosis tag-mycolic-acids tag-pathogenesis tag-tb-treatment tag-tuberculosis" itemtype="https://schema.org/CreativeWork" itemscope> <div class="inside-article"> <div class="featured-image page-header-image-single "> <img width="1200" height="628" src="https://infect.blog/archive/wp-content/uploads/2024/10/banner-21-01-min-scaled-e1730097057742.jpg" class="attachment-full size-full" alt="" itemprop="image" decoding="async" fetchpriority="high" /> </div> <header class="entry-header"> <h1 class="entry-title" itemprop="headline">The Role of the Mycobacterial Cell Wall in Disease Pathogenesis</h1> <div class="entry-meta"> <span class="posted-on"><time class="entry-date published" datetime="2024-10-28T12:01:08+05:30" itemprop="datePublished">October 28, 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;"> The cell wall of the Mycobacterium species, specifically Mycobacterium tuberculosis, Mtb, plays a critical role in its success as a pathogen, in its ability to resist treatment, and in its persistence in the host organism. Unlike most other bacterial cell walls, the mycobacterial cell wall is unusually complex and studied, and this contributes to the pathogen&#8217;s resilience to antibiotics and host immune responses. Such a unique structure not only provides physical protection to the bacterium from external attacks but is also actively involved in the pathogenesis of TB through interactions with host cells and modulation of the host&#8217;s immune response. Knowing the structure and functions of the cell wall of mycobacteria is therefore crucial in developing new therapeutic strategies against TB, which remains one of the most deadly infectious diseases worldwide. </span></p> <h3><b>Mycobacterial cell wall composition and structure</b></h3> <p><span style="font-weight: 400;">The mycobacterial cell wall is a complex assembly of lipids, proteins, and polysaccharides, hence much different from any other known bacterial cell walls. It is composed of three major layers: a peptidoglycan layer, an arabinogalactan layer, and a mycolic acid layer, making the bacterium impermeable and therefore resistant to many antibiotics. The peptidoglycan refers to structural rigidity, while the arabinogalactan links the peptidoglycan to the outer layer of mycolic acid, which is responsible for the cell wall&#8217;s hydrophobicity and resistance to chemical damage.</span></p> <p><span style="font-weight: 400;">Mycolic acids are long-chain fatty acids that form a waxy coating around the cell, making the mycobacterial cell wall among the most lipid-enriched structures in nature. The waxy coat is crucial for the survival of the bacterium in hostile environments encountered inside immune cells, the macrophages, within the host. Other than that, other kinds of lipids are also present on the cell wall, such as phosphatidylinositol mannosides and lipoarabinomannan, which are essential in the modulation of immunity.</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/pathogenesis" target="_blank" title="pathogenesis - yearwise publication trends">pathogenesis</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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The complex structure of the cell wall enables Mtb to evade the host immune system, survive under hostile conditions, and persist in latent form for years. Partly, this is because the cell wall prevents phagosomes, vesicles that engulf bacteria, from fusing with lysosomes, vesicles containing digestive enzymes, in the macrophages. Such inhibition in fusion prevents the killing of Mtb; instead, it replicates within the macrophage.</span></p> <p><span style="font-weight: 400;">Moreover, cell wall components such as mycolic acids, LAMs, and other glycolipids modulate the host immune response. For instance, LAMs have been shown to downregulate the production of pro-inflammatory cytokines, which play an important role in mounting an efficient immune response. If the host&#8217;s immune response is damaged, the Mtb will not be detected and thus will not be destroyed, finally establishing itself, thereby establishing persistent infection. Owing to its potential interference with the induction of protective immunity, TB becomes a chronic, previous complication with high mortality if untreated.</span></p> <h3><b>Cell Wall Biosynthesis as a Drug Target</b></h3> <p><span style="font-weight: 400;">Since the cell wall plays such a cardinal role in the survival and pathogenicity of Mtb, it is an attractive drug target. Inhibiting the biosynthesis of cell wall components can render the bacterium more susceptible to antibiotics and the host immune system. The current drugs against TB, including isoniazid and ethambutol, act against enzymes involved in mycolic acid and arabinogalactan biosynthesis, respectively. It is in view of emerging strains of drug-resistant TB that new drugs targeting other aspects of the cell wall biosynthesis process need to be developed. With the acidity of recent advances in molecular genetics and biochemistry, several potential targets within the cell wall biosynthesis pathway have been identified over the past decade.</span></p> <p><span style="font-weight: 400;">These include enzymes involved in the early stages of peptidoglycan synthesis and others responsible for mycolic acid and LAM biosynthesis. Inhibitors of these enzymes could, therefore, disrupt the formation of the cell wall and result in bacterial death. The next strategy is the development of drugs that target the transport and assembly of components of the cell wall. If key lipids are unable to transport efficiently to the cell surface, it may be possible to weaken the cell wall and enhance the efficacy of existing treatments for TB.</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/pathogenesis" target="_blank" rel="noopener" title="pathogenesis - yearwise publication list">pathogenesis</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; border-radius:30px; } .publication-block p { margin-bottom: .5em; font-size: 15px; color: #000; } h3 { font-size: 18px !important; margin-bottom: 20px; line-height: 1.2em; font-weight: 600; text-transform: none; } a { padding: 5px; color: #a71c49; } #keyword-papers{ margin-top: 20px; text-align: center; } </style> <script> function decodeString(str) { str = str.replace(/\\'/g, "'"); str = str.replace(/\\'/g, "'"); str = str.replace(/\\'/g, "'"); return str; } function displayResults_recent(papers) { var resultsContainer = document.getElementById('results_recent'); if (!papers || papers.length === 0) { resultsContainer.innerHTML = '<p>No recent publications found.</p>'; return; } papers.forEach(paper => { var publicationBlock = document.createElement('div'); publicationBlock.className = 'publication-block'; var title_de = decodeString(paper.title); var publicationHTML = ` <div style="margin-bottom: 10px;line-height: 24px;"><a href="${paper.url}" target="_blank" title="${title_de}">${title_de}</a></div> <p><strong>Issue Release:</strong> ${paper.publishedDate}</p> `; publicationBlock.innerHTML = publicationHTML; resultsContainer.appendChild(publicationBlock); }); } function displayKeywordPapers(keywords) { var resultsContainer = document.getElementById('keyword-papers'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach((key, index) => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://infect.blog/recent-publications/index/${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": "Zebrafish as a Model for Investigating Antiviral Innate Immunity.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39192133", "publishedDate": "2025" }, { "title": "Domain 5 of Beta 2 glycoprotein I: Friend or foe in health? Context matters.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38917928", "publishedDate": "2024" }, { "title": "Mitochondrial homeostasis in odontoblast: Physiology, pathogenesis and targeting strategies.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38917871", "publishedDate": "2024" }, { "title": "Astrocyte-secreted C3 signaling impairs neuronal development and cognition in autoimmune diseases.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38945516", "publishedDate": "2024" }, { "title": "Single-cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946005", "publishedDate": "2024" }, { "title": "Diosgenin attenuates metabolic-associated fatty liver disease through the hepatic NLRP3 inflammasome-dependent signaling pathway.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38944952", "publishedDate": "2024" }, { "title": "Temperature-responsive hydrogel-grafted vessel-on-a-chip: Exploring cold-induced endothelial injury.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946677", "publishedDate": "2024" }, { "title": "Dihydromyricetin ameliorates diabetic renal fibrosis via regulating SphK1 to suppress the activation of NF-\u03baB pathway.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38945289", "publishedDate": "2024" }, { "title": "A Rare Case of Thoracic SMARCA4-Deficient Undifferentiated Tumor With Diffuse Brain Metastasis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38947666", "publishedDate": "2024" }, { "title": "Isothiocyanate-Corticosteroid Conjugates against asthma: Unity makes strength.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38944936", "publishedDate": "2024" }, { "title": "Identification of diagnostic signature and immune microenvironment subtypes of venous thromboembolism.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38945040", "publishedDate": "2024" }, { "title": "Recurrent Cerebral Hemorrhaging with Platelet Dysfunction Accompanied by Anti-glycoprotein VI Autoantibodies in a Patient with TAFRO Syndrome.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38945933", "publishedDate": "2024" }, { "title": "Causal relationship between infection and IgA nephropathy: a bidirectional two-sample mendelian randomization study.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946159", "publishedDate": "2024" }, { "title": "[Clinical characteristics and genetic analysis of two children with X-linked Centronuclear myopathy due to variants of MTM1 gene].", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946363", "publishedDate": "2024" }, { "title": "Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946541", "publishedDate": "2024" }, { "title": "Suppression of MyD88 disturbs gut microbiota and activates the NLR pathway and hence fails to ameliorate DSS-induced colitis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946731", "publishedDate": "2024" }, { "title": "GNL3L exhibits pro-tumor activities via NF-\u03baB pathway as a poor prognostic factor in acute myeloid leukemia.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38947394", "publishedDate": "2024" }, { "title": "Single-nucleus transcriptomics reveals adrenergic and STAT3 signaling in paradoxical low-flow low-gradient -specific cardiomyocyte subclusters: implications for aortic stenosis pathogenesis and treatment.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38943668", "publishedDate": "2024" }, { "title": "Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38944808", "publishedDate": "2024" }, { "title": "MiR-98-3p alleviates lipopolysaccharide-induced pulmonary microvascular endothelial barrier dysfunction by targeting DKK3 in sepsis-induced acute lung injury.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38945840", "publishedDate": "2024" } ]; var keywordsArray = ["Mycobacterium tuberculosis","cell wall","pathogenesis","tuberculosis","mycolic acids","LAM","drug resistance","biosynthesis","immune evasion","TB treatment"]; displayResults_recent(recent_papers); displayKeywordPapers(keywordsArray); // function stripslashes(str) { // if (typeof str === 'string') { // return str.replace(/\/g, ''); // } // } </script></p> <h3><b>Challenges of Targeting Mycobacterial Cell Walls</b></h3> <p><span style="font-weight: 400;">While the mycobacterial cell wall represents an attractive drug target, there are formidable challenges to be overcome. The cell wall biosynthetic pathways themselves are intrinsically complex and redundant, so inhibiting one enzyme or pathway alone may not be sufficient to kill the bacterium. Mtb has developed compensatory mechanisms that enable it to survive even in the presence of drugs by compensating for the inhibition of one pathway. Furthermore, one of the major problems associated with drug delivery is the impermeability of the cell wall. Many potentially useful drugs will not be able to go through the layers of lipids that comprise the cell wall and therefore will not work.</span></p> <p><span style="font-weight: 400;">Researchers are trying out combination therapies that target more than one component of cell wall biosynthesis pathways in an effort to prevent the bacterium from compensating for the inhibition of a single target. Novel delivery systems, such as nanoparticles, could be developed to ensure better penetration of drugs into the mycobacterial cell wall; this could probably improve their efficacy.</span></p> <h3><b>Conclusion</b></h3> <p><span style="font-weight: 400;">It is the mycobacterial cell wall, one of the most powerful structures in the pathogenesis of tuberculosis. Its complex structure and functions give Mycobacterium tuberculosis resistance to a wide range of antibiotics and equip it with the possibility of including the host&#8217;s immune system, allowing this typical opportunity pathogen to persist in the human body for years. In such a scenario, knowledge of the intricacies of cell wall biosynthesis and its involvement in disease pathogenesis is very important for developing new therapeutic strategies against TB. Though the challenges in this research area are huge, continuous study on the molecular mechanisms of cell wall assembly and function give hope for a more effective mode of therapy against this killing disease.</span></p> <p></p> <h3><b>References</b></h3> <ol> <li>Kolattukudy, P.E., Fernandes, N.D., Azad, A.K., Fitzmaurice, A.M. and Sirakova, T.D., 1997. <a href="https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2958.1997.3361705.x">Biochemistry and molecular genetics of cell‐wall lipid biosynthesis in mycobacteria.</a> <i>Molecular microbiology</i>, <i>24</i>(2), pp.263-270.</li> <li>Belisle, J.T., Vissa, V.D., Sievert, T., Takayama, K., Brennan, P.J. and Besra, G.S., 1997. <a href="https://www.science.org/doi/abs/10.1126/science.276.5317.1420">Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis.</a> <i>Science</i>, <i>276</i>(5317), pp.1420-1422.</li> <li>Blattner, F.R., Plunkett III, G., Bloch, C.A., Perna, N.T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J.D., Rode, C.K., Mayhew, G.F. and Gregor, J., 1997. <a href="https://www.science.org/doi/abs/10.1126/science.277.5331.1453">The complete genome sequence of Escherichia coli K-12.</a> <i>science</i>, <i>277</i>(5331), pp.1453-1462.</li> <li>Sreevatsan, S., Pan, X.I., Stockbauer, K.E., Connell, N.D., Kreiswirth, B.N., Whittam, T.S. and Musser, J.M., 1997. <a href="https://www.pnas.org/doi/abs/10.1073/pnas.94.18.9869">Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination.</a> <i>Proceedings of the National Academy of Sciences</i>, <i>94</i>(18), pp.9869-9874.</li> <li>Smith, D.R., Richterich, P., Rubenfield, M., Rice, P.W., Butler, C., Lee, H.M., Kirst, S., Gundersen, K., Abendschan, K., Xu, Q. and Chung, M., 1997. <a href="https://genome.cshlp.org/content/7/8/802.short">Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.</a> <i>Genome research</i>, <i>7</i>(8), pp.802-819.</li> <li>Philipp, W.J., Poulet, S., Eiglmeier, K., Pascopella, L., Balasubramanian, V., Heym, B., Bergh, S., Bloom, B.R., Jacobs Jr, W.R. and Cole, S.T., 1996. <a href="https://www.pnas.org/doi/abs/10.1073/pnas.93.7.3132">An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis H37Rv, and comparison with Mycobacterium leprae.</a> <i>Proceedings of the National Academy of Sciences</i>, <i>93</i>(7), pp.3132-3137.</li> <li>Gobin, J., Moore, C.H., Reeve Jr, J.R., Wong, D.K., Gibson, B.W. and Horwitz, M.A., 1995. <a href="https://www.pnas.org/doi/abs/10.1073/pnas.92.11.5189">Iron acquisition by Mycobacterium tuberculosis: isolation and characterization of a family of iron-binding exochelins.</a> <i>Proceedings of the National Academy of Sciences</i>, <i>92</i>(11), pp.5189-5193.</li> </ol> <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>Top Experts on “<b style="color:#000;font-size:22px;">pathogenesis</b>“</h2> </div> </div><div class="author-main"><div id="results_author"></div><div style="text-align: center;"><a class="register-button" href="https://infect.blog/expert-search" target="_blank" rel="noopener">Find experts on any field</a></div></div><div class="inside-article" style="background: none;border: none;box-shadow: none;margin-top: -70px;"> <style> .author-block { padding: 15px; 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", "email": "ruggeri@scripps.edu", "slug_tail": "z-ruggeri" } }; //console.log(authors_data); displayResults_author(authors_data); var keywordsArray = ["Mycobacterium tuberculosis","cell wall","pathogenesis","tuberculosis","mycolic acids","LAM","drug resistance","biosynthesis","immune evasion","TB treatment"]; displayKeywordAuthors(keywordsArray); </script></p> </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/pathogenesis/" rel="category tag">Pathogenesis</a></span> <span class="tags-links"><span class="gp-icon 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