{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:42:39Z","timestamp":1791988959605,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010121","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000}}],"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"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":["F32 AI143203"],"award-info":[{"award-number":["F32 AI143203"]}],"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":["R01 AI153332"],"award-info":[{"award-number":["R01 AI153332"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"national institute of neurological disorders and stroke","doi-asserted-by":"publisher","award":["R01 NS116716"],"award-info":[{"award-number":["R01 NS116716"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"coordena\u00e7\u00e3o de aperfei\u00e7oamento de pessoal de n\u00edvel superior","doi-asserted-by":"publisher","award":["Finance code 001"],"award-info":[{"award-number":["Finance code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Type VII secretion systems (T7SS) have been identified in Actinobacteria and Firmicutes and have been shown to secrete effector proteins with functions in virulence, host toxicity, and\/or interbacterial killing in a few genera. Bioinformatic analysis indicates that isolates of Group B\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    (GBS) encode at least four distinct subtypes of T7SS machinery, three of which encode adjacent putative T7SS effectors with WXG and LXG motifs. However, the function of T7SS in GBS pathogenesis is unknown. Here we assessed the role of the most abundant GBS T7SS subtype during GBS pathogenesis. In a murine model of hematogenous meningitis, mice infected with GBS lacking a functional T7SS or lacking the secreted WXG100 effector EsxA exhibited less mortality, lower bacterial burdens in tissues, and decreased inflammation in the brain compared to mice infected with the parental GBS strain. We further showed that this T7SS induces cytotoxicity in brain endothelium and that EsxA contributes to these cytotoxicity phenotypes in a WXG motif-dependent manner. Finally, we determined that EsxA is a pore-forming protein, thus demonstrating the first role for a non-mycobacterial EsxA homolog in pore formation. This work reveals the importance of a T7SS in host\u2013GBS interactions and has implications for T7SS effector function in other Gram-positive bacteria.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010121","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T13:33:28Z","timestamp":1638797608000},"page":"e1010121","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-6403","authenticated-orcid":true,"given":"Brady L.","family":"Spencer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7907-3840","authenticated-orcid":true,"given":"Uday","family":"Tak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica C.","family":"Mendon\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prescilla E.","family":"Nagao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-8092","authenticated-orcid":true,"given":"Michael","family":"Niederweis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4232-6837","authenticated-orcid":true,"given":"Kelly S.","family":"Doran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"issue":"1","key":"ppat.1010121.ref001","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.VMBF-0012-2015","article-title":"Bacterial Secretion Systems: An Overview.","volume":"4","author":"ER Green","year":"2016","journal-title":"Microbiol Spectr."},{"issue":"Suppl 1","key":"ppat.1010121.ref002","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1471-2180-9-S1-S2","article-title":"Protein secretion systems in bacterial-host associations, and their description in the Gene Ontology","volume":"9","author":"TT Tseng","year":"2009","journal-title":"BMC Microbiol"},{"issue":"11","key":"ppat.1010121.ref003","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nrmicro1773","article-title":"Type VII secretion\u2014mycobacteria show the way","volume":"5","author":"AM Abdallah","year":"2007","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"ppat.1010121.ref004","doi-asserted-by":"crossref","first-page":"e89313","DOI":"10.1371\/journal.pone.0089313","article-title":"WXG100 protein superfamily consists of three subfamilies and exhibits an alpha-helical C-terminal conserved residue pattern.","volume":"9","author":"C Poulsen","year":"2014","journal-title":"PLoS One"},{"issue":"14","key":"ppat.1010121.ref005","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1038\/sj.emboj.7600732","article-title":"Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6","volume":"24","author":"PS Renshaw","year":"2005","journal-title":"EMBO J"},{"issue":"11","key":"ppat.1010121.ref006","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nrmicro.2016.131","article-title":"ESX secretion systems: mycobacterial evolution to counter host immunity","volume":"14","author":"MI 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