Comprehensive Pan-Genome Analysis of Mycobacterium marinum: Insights into Genomic Diversity, Evolution, and Pathogenicity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comprehensive Pan-Genome Analysis of Mycobacterium marinum: Insights into Genomic Diversity, Evolution, and Pathogenicity Meng Zhang, Sabir Adroub, Roy Ummels, Mohammed Asaad, Lei Song, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4531738/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Nov, 2024 Read the published version in Scientific Reports → Version 1 posted 15 You are reading this latest preprint version Abstract Mycobacteria is a diverse genus that includes both innocuous environmental species and serious pathogens like Mycobacterium tuberculosis , Mycobacterium leprae , and Mycobacterium ulcerans , the causative agents of tuberculosis, leprosy, and Buruli ulcer, respectively. This study focuses on M. marinum , a closely related species known for its larger genome and ability to infect ectothermic species and cooler human extremities. Utilizing whole-genome sequencing, we conducted a comprehensive pan-genome analysis of 100 M. marinum strains, exploring genetic diversity and its impact on pathogenesis and host specificity. Our findings highlight significant genomic diversity, with clear distinctions in core, dispensable, and unique genes among the isolates. Phylogenetic analysis revealed a broad distribution of genetic lineages, challenging previous classifications into distinct clades. Additionally, we examined the synteny and diversity of the virulence factor CpnT, noting a wide range of C-terminal domain variations across strains, which points to potential adaptations in pathogenic mechanisms. This study enhances our understanding of M. marinum 's genomic architecture and its evolutionary relationship with other mycobacterial pathogens, providing insights that could inform disease control strategies for M. tuberculosis and other mycobacteria. Biological sciences/Microbiology/Bacteria/Bacterial genetics Biological sciences/Microbiology/Bacteria/Bacterial genomics Mycobacterium marinum Pan genome Evolution Virulence genes Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigureS1.jpg SupplementaryFigureS2.jpg SupplementaryFigureS3.jpg SupplementaryFigureS4.jpg SupplementaryFigureS5.jpg SupplementaryFigures.doc SupplementaryTableS1.xls SupplementaryTableS2.xls SupplementaryTableS3.xls SupplementaryTableS4.xls SupplementaryTableS5.xls Cite Share Download PDF Status: Published Journal Publication published 12 Nov, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 08 Jul, 2024 Reviews received at journal 08 Jul, 2024 Reviews received at journal 30 Jun, 2024 Reviews received at journal 27 Jun, 2024 Reviewers agreed at journal 18 Jun, 2024 Reviewers agreed at journal 18 Jun, 2024 Reviewers agreed at journal 18 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers invited by journal 17 Jun, 2024 Editor assigned by journal 17 Jun, 2024 Editor invited by journal 09 Jun, 2024 Submission checks completed at journal 06 Jun, 2024 First submitted to journal 05 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4531738","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":316010240,"identity":"c62a072d-6eb5-4406-87d1-3df068616df5","order_by":0,"name":"Meng Zhang","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Meng","middleName":"","lastName":"Zhang","suffix":""},{"id":316010241,"identity":"c174ba4d-cd60-4969-a0c0-feca3b738117","order_by":1,"name":"Sabir Adroub","email":"","orcid":"","institution":"King Abdullah University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Sabir","middleName":"","lastName":"Adroub","suffix":""},{"id":316010242,"identity":"1ef4dfb3-335e-4a0f-92be-e7d0f16b7a2c","order_by":2,"name":"Roy Ummels","email":"","orcid":"","institution":"Amsterdam UMC, Location VU Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Roy","middleName":"","lastName":"Ummels","suffix":""},{"id":316010243,"identity":"59bc546a-9307-411a-864f-862086e289ac","order_by":3,"name":"Mohammed Asaad","email":"","orcid":"","institution":"Qatar University (QU) Health, Qatar University","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"","lastName":"Asaad","suffix":""},{"id":316010245,"identity":"c06b47b1-b311-4c9e-b8ac-b2871ffeb5af","order_by":4,"name":"Lei Song","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Song","suffix":""},{"id":316010246,"identity":"bab44fa4-8ae1-400e-a98d-9cd9735755d4","order_by":5,"name":"Arnab Pain","email":"","orcid":"","institution":"King Abdullah University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Arnab","middleName":"","lastName":"Pain","suffix":""},{"id":316010247,"identity":"2dd1c595-dd62-414d-9fbb-cc12f26463d9","order_by":6,"name":"Wilbert Bitter","email":"","orcid":"","institution":"Amsterdam UMC, Location VU Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Wilbert","middleName":"","lastName":"Bitter","suffix":""},{"id":316010248,"identity":"039dd3d1-c51a-49df-a02b-242415f7bb8e","order_by":7,"name":"Qingtian Guan","email":"","orcid":"","institution":"The First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Qingtian","middleName":"","lastName":"Guan","suffix":""},{"id":316010249,"identity":"fa150ff1-2418-4035-80af-acd5d1a0c4bd","order_by":8,"name":"Abdallah M. Abdallah","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYBACNgkGA4YHBQwJEG4FmDTAq4UfpCXBAKblDBFaJGcga2FsI0KLwe3mjR8SDOzyGMTOGH/4Oc86sYG9eZsEQ5kdbi13jhVLJBgkFzNI55hJ9m5LT2zgOVYmwXAuGbeWGzkGQC3MiQ1ALQy82w4nNkjkmEkwtjHj1GJ/I8f4R4JBPUiL8ce/c4Ba5N+AtNTjs8UMaMthkBYDad4GkC08IC2H8fmlzCLB4Hhim3RambTMsXTjNp60YouEc8dxa7ndvPnGh4rqxH7p5M0f39RYy/azH95440NZNU4tcMAGoZghjAQ2wjpgABZQJGgZBaNgFIyCYQ8A+JBSk4nnNl8AAAAASUVORK5CYII=","orcid":"","institution":"Qatar University (QU) Health, Qatar University","correspondingAuthor":true,"prefix":"","firstName":"Abdallah","middleName":"M.","lastName":"Abdallah","suffix":""}],"badges":[],"createdAt":"2024-06-05 06:12:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4531738/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4531738/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-75228-0","type":"published","date":"2024-11-12T15:58:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":69285262,"identity":"12c54959-606f-4e3d-9f66-0229532b14c9","added_by":"auto","created_at":"2024-11-18 19:25:06","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":998808,"visible":true,"origin":"","legend":"","description":"","filename":"MMpangenomeManuscriptv20240605AM.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1_covered_8f87806a-5244-4052-b684-5f9f6b5d498c.pdf"},{"id":58755496,"identity":"34f7139e-d78a-437c-a924-bcba2eb41dc8","added_by":"auto","created_at":"2024-06-20 16:57:21","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":6785080,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/61278e8da2d02088239403ab.jpg"},{"id":58755181,"identity":"f2f23a9d-db26-4b08-87cd-6f2f7d56707a","added_by":"auto","created_at":"2024-06-20 16:49:21","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":2106196,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/d90577015721a74b7b6e9bb8.jpg"},{"id":58755180,"identity":"0b340334-00ac-4e57-86c4-20dea8cd015e","added_by":"auto","created_at":"2024-06-20 16:49:21","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":5201884,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/cbec6fdc23e1a10038b06702.jpg"},{"id":58755185,"identity":"3eb081bf-f48e-4796-bcac-260b1ca64605","added_by":"auto","created_at":"2024-06-20 16:49:21","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":2670221,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/81793d7f3f75689b25bcbf8b.jpg"},{"id":58755183,"identity":"ccea08d4-ceab-48ad-89d9-b4a9d1f67944","added_by":"auto","created_at":"2024-06-20 16:49:21","extension":"jpg","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":7739708,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureS5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/525c3b39ef8eb5144890f369.jpg"},{"id":58755192,"identity":"7fe4cd8b-8555-4214-b0e7-82a0df871e89","added_by":"auto","created_at":"2024-06-20 16:49:22","extension":"doc","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":24731136,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigures.doc","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/4a7f3f430747afa64d6bc9df.doc"},{"id":58755497,"identity":"9c30ca90-686f-437c-918f-b800f4758b2e","added_by":"auto","created_at":"2024-06-20 16:57:21","extension":"xls","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":39424,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS1.xls","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/c4507e851db65e9b1d4391a7.xls"},{"id":58755498,"identity":"7d7372e4-aa00-49c6-9648-250bc06d955c","added_by":"auto","created_at":"2024-06-20 16:57:21","extension":"xls","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":40960,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS2.xls","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/d91dae523de13521c0c41059.xls"},{"id":58755190,"identity":"da516389-2dee-4c63-b0c7-d766e924f69f","added_by":"auto","created_at":"2024-06-20 16:49:21","extension":"xls","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":85504,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS3.xls","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/6ed5276579e320f2325cb19e.xls"},{"id":58755191,"identity":"f5612ccd-d2b5-4da4-96e2-682a09001f80","added_by":"auto","created_at":"2024-06-20 16:49:21","extension":"xls","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":75776,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS4.xls","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/16a5532ff64431716a6d7187.xls"},{"id":58755189,"identity":"9a67b95f-eb7b-4fca-9e11-6a439dc6ce8c","added_by":"auto","created_at":"2024-06-20 16:49:21","extension":"xls","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":119296,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS5.xls","url":"https://assets-eu.researchsquare.com/files/rs-4531738/v1/d8fb517e45576789f1687854.xls"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comprehensive Pan-Genome Analysis of Mycobacterium marinum: Insights into Genomic Diversity, Evolution, and Pathogenicity","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Mycobacterium marinum, Pan genome, Evolution, Virulence genes","lastPublishedDoi":"10.21203/rs.3.rs-4531738/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4531738/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMycobacteria is a diverse genus that includes both innocuous environmental species and serious pathogens like \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e, \u003cem\u003eMycobacterium leprae\u003c/em\u003e, and \u003cem\u003eMycobacterium ulcerans\u003c/em\u003e, the causative agents of tuberculosis, leprosy, and Buruli ulcer, respectively. This study focuses on \u003cem\u003eM. marinum\u003c/em\u003e, a closely related species known for its larger genome and ability to infect ectothermic species and cooler human extremities. Utilizing whole-genome sequencing, we conducted a comprehensive pan-genome analysis of 100 \u003cem\u003eM. marinum\u003c/em\u003e strains, exploring genetic diversity and its impact on pathogenesis and host specificity. Our findings highlight significant genomic diversity, with clear distinctions in core, dispensable, and unique genes among the isolates. Phylogenetic analysis revealed a broad distribution of genetic lineages, challenging previous classifications into distinct clades. Additionally, we examined the synteny and diversity of the virulence factor CpnT, noting a wide range of C-terminal domain variations across strains, which points to potential adaptations in pathogenic mechanisms. This study enhances our understanding of \u003cem\u003eM. marinum\u003c/em\u003e's genomic architecture and its evolutionary relationship with other mycobacterial pathogens, providing insights that could inform disease control strategies for \u003cem\u003eM. tuberculosis\u003c/em\u003e and other mycobacteria.\u003c/p\u003e","manuscriptTitle":"Comprehensive Pan-Genome Analysis of Mycobacterium marinum: Insights into Genomic Diversity, Evolution, and Pathogenicity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-20 16:49:16","doi":"10.21203/rs.3.rs-4531738/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-09T01:57:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-08T14:05:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-30T21:56:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-27T07:44:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293389047210289007645184304003742132813","date":"2024-06-18T15:47:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140633697187930754904081341919213971904","date":"2024-06-18T13:46:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21179404371405160200989958950562017997","date":"2024-06-18T12:20:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"79679874314778335218140563248299215956","date":"2024-06-17T22:47:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3610904398243407450291388035950960319","date":"2024-06-17T22:23:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39498933382875635772793875665384534740","date":"2024-06-17T17:21:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-17T10:16:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-17T09:56:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-09T15:43:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-06T09:42:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-06-05T06:11:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0c701bc3-6b7f-492e-ad43-57e4331183cd","owner":[],"postedDate":"June 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":33417931,"name":"Biological sciences/Microbiology/Bacteria/Bacterial genetics"},{"id":33417932,"name":"Biological sciences/Microbiology/Bacteria/Bacterial genomics"}],"tags":[],"updatedAt":"2024-11-18T19:18:16+00:00","versionOfRecord":{"articleIdentity":"rs-4531738","link":"https://doi.org/10.1038/s41598-024-75228-0","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-11-12 15:58:12","publishedOnDateReadable":"November 12th, 2024"},"versionCreatedAt":"2024-06-20 16:49:16","video":"","vorDoi":"10.1038/s41598-024-75228-0","vorDoiUrl":"https://doi.org/10.1038/s41598-024-75228-0","workflowStages":[]},"version":"v1","identity":"rs-4531738","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4531738","identity":"rs-4531738","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.