{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:14:03Z","timestamp":1790183643963,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014156","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000}}],"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE030121"],"award-info":[{"award-number":["R01DE030121"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03DE034511"],"award-info":[{"award-number":["R03DE034511"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CCTR Endowment Fund","award":["CCTR Endowment Fund"],"award-info":[{"award-number":["CCTR Endowment Fund"]}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R21DE034103"],"award-info":[{"award-number":["R21DE034103"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["P30 CA016059"],"award-info":[{"award-number":["P30 CA016059"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Infective endocarditis (IE) is a life-threatening disease most often caused by blood-borne bacteria that infect previously damaged cardiac tissue. Despite the importance of this disease, the genetic basis for IE-associated fitness remains poorly defined. Here, we present the first genome-wide\n                    <jats:italic>in vivo<\/jats:italic>\n                    analysis of bacterial fitness in a vertebrate model of IE. We identified 146 genes in\n                    <jats:italic>Streptococcus sanguinis<\/jats:italic>\n                    required for IE fitness, the majority of which had not previously been linked to endocarditis. These determinants cluster into conserved metabolic, cell envelope, transport, and regulatory pathways, representing a vast reservoir of potential targets for novel antimicrobial intervention. A subset of these genes was examined in\n                    <jats:italic>Streptococcus mutans<\/jats:italic>\n                    ; all were found to be essential for IE fitness in this distantly related oral species as well, suggesting broad conservation. Using experimental evolution, we further show that disruption of key fitness pathways triggers reproducible compensatory \u201cbypass\u201d mechanisms. Together, these findings provide a comprehensive, genome-wide map of the bacterial niche-requirements for streptococcal infective endocarditis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014156","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:33:52Z","timestamp":1786988032000},"page":"e1014156","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A genome-wide in vivo screen reveals fitness pathways required for streptococcal infective endocarditis"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0228-6124","authenticated-orcid":true,"given":"Liang","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vysakh","family":"Anandan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna M.","family":"Tyc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephina Anna","family":"Vossen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery-francine","family":"Assi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine Somia","family":"Benbei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicai","family":"Zollar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-7583","authenticated-orcid":true,"given":"Todd","family":"Kitten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ppat.1014156.ref001","doi-asserted-by":"crossref","first-page":"16059","DOI":"10.1038\/nrdp.2016.59","article-title":"Infective endocarditis","volume":"2","author":"TL Holland","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"10","key":"ppat.1014156.ref002","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41569-019-0215-0","article-title":"Infective endocarditis: innovations in the management of an old disease","volume":"16","author":"B Iung","year":"2019","journal-title":"Nat Rev Cardiol"},{"issue":"10450","key":"ppat.1014156.ref003","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0140-6736(24)01098-5","article-title":"Infective endocarditis","volume":"404","author":"M Li","year":"2024","journal-title":"Lancet"},{"key":"ppat.1014156.ref004","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.amjcard.2023.07.127","article-title":"30-Year Trends of Incidence and Mortality of Infective Endocarditis in the United States-Unveiling the Age- and Gender-Related and Regional Disparities","volume":"204","author":"SS Taduru","year":"2023","journal-title":"Am J Cardiol"},{"issue":"1","key":"ppat.1014156.ref005","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrcardio.2013.174","article-title":"Mechanisms of infective endocarditis: pathogen-host interaction and risk states","volume":"11","author":"K Werdan","year":"2014","journal-title":"Nat Rev Cardiol"},{"issue":"7","key":"ppat.1014156.ref006","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1086\/339604","article-title":"Formation of vegetations during infective endocarditis excludes binding of bacterial-specific host antibodies to Enterococcus faecalis","volume":"185","author":"JK McCormick","year":"2002","journal-title":"J Infect Dis"},{"key":"ppat.1014156.ref007","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/path.1711150204","article-title":"Experimental bacterial endocarditis. 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