{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:47:08Z","timestamp":1791532028730,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009116","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000}}],"reference-count":141,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08AI132555"],"award-info":[{"award-number":["K08AI132555"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI147511"],"award-info":[{"award-number":["R21AI147511"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI147511"],"award-info":[{"award-number":["R21AI147511"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI143290"],"award-info":[{"award-number":["R01AI143290"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010559","name":"Children's Hospital of Pittsburgh","doi-asserted-by":"publisher","award":["Children's Trust Young Investigator Award"],"award-info":[{"award-number":["Children's Trust Young Investigator Award"]}],"id":[{"id":"10.13039\/100010559","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000915","name":"Richard King Mellon Foundation","doi-asserted-by":"publisher","award":["Pilot Award"],"award-info":[{"award-number":["Pilot Award"]}],"id":[{"id":"10.13039\/100000915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007408","name":"Medical Center, University of Pittsburgh","doi-asserted-by":"publisher","award":["i4Kids Pilot Award"],"award-info":[{"award-number":["i4Kids Pilot Award"]}],"id":[{"id":"10.13039\/100007408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Streptococcus agalactiae<\/jats:italic>\n                    (group B\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    ; GBS) remains a dominant cause of serious neonatal infections. One aspect of GBS that renders it particularly virulent during the perinatal period is its ability to invade the chorioamniotic membranes and persist in amniotic fluid, which is nutritionally deplete and rich in fetal immunologic factors such as antimicrobial peptides. We used next-generation sequencing of transposon-genome junctions (Tn-seq) to identify five GBS genes that promote survival in the presence of human amniotic fluid. We confirmed our Tn-seq findings using a novel CRISPR inhibition (CRISPRi) gene expression knockdown system. This analysis showed that one gene, which encodes a GntR-class transcription factor that we named MrvR, conferred a significant fitness benefit to GBS in amniotic fluid. We generated an isogenic targeted deletion of the\n                    <jats:italic>mrvR<\/jats:italic>\n                    gene, which had a growth defect in amniotic fluid relative to the wild type parent strain. The\n                    <jats:italic>mrvR<\/jats:italic>\n                    deletion strain also showed a significant biofilm defect\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Subsequent\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies showed that while the mutant was able to cause persistent murine vaginal colonization, pregnant mice colonized with the\n                    <jats:italic>mrvR<\/jats:italic>\n                    deletion strain did not develop preterm labor despite consistent GBS invasion of the uterus and the fetoplacental units. In contrast, pregnant mice colonized with wild type GBS consistently deliver prematurely. In a sepsis model the\n                    <jats:italic>mrvR<\/jats:italic>\n                    deletion strain showed significantly decreased lethality. In order to better understand the mechanism by which this newly identified transcription factor controls GBS virulence, we performed RNA-seq on wild type and\n                    <jats:italic>mrvR<\/jats:italic>\n                    deletion GBS strains, which revealed that the transcription factor affects expression of a wide range of genes across the GBS chromosome. Nucleotide biosynthesis and salvage pathways were highly represented among the set of differentially expressed genes, suggesting that MrvR may be involved in regulating nucleotide availability.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009116","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T13:34:22Z","timestamp":1615210462000},"page":"e1009116","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Genome-Wide fitness analysis of group B Streptococcus in human amniotic fluid reveals a transcription factor that controls multiple virulence traits"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-4196","authenticated-orcid":true,"given":"Allison N.","family":"Dammann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3071-7809","authenticated-orcid":true,"given":"Anna B.","family":"Chamby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Catomeris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-1344","authenticated-orcid":true,"given":"Kyle M.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-3257","authenticated-orcid":true,"given":"Herv\u00e9","family":"Tettelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-5726","authenticated-orcid":true,"given":"Jan-Peter","family":"van Pijkeren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-1841","authenticated-orcid":true,"given":"Kathyayini P.","family":"Gopalakrishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1627-3532","authenticated-orcid":true,"given":"Mary F.","family":"Keith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8784-4737","authenticated-orcid":true,"given":"Jordan L.","family":"Elder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1761-794X","authenticated-orcid":true,"given":"Adam J.","family":"Ratner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1959-186X","authenticated-orcid":true,"given":"Thomas A.","family":"Hooven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"ppat.1009116.ref001","article-title":"Neonatal infections: group B streptococcus.","volume":"2014","author":"PT Heath","year":"2014","journal-title":"BMJ clinical evidence"},{"key":"ppat.1009116.ref002","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nrmicro1552","article-title":"Group B Streptococcus: global incidence and vaccine development","volume":"4","author":"AK Johri","year":"2006","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1009116.ref003","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/jp.2011.40","article-title":"Early-onset neonatal 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