{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T18:05:08Z","timestamp":1784570708818,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014434","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AI180089"],"award-info":[{"award-number":["AI180089"]}]},{"name":"NIH","award":["AI153071"],"award-info":[{"award-number":["AI153071"]}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["PATH"],"award-info":[{"award-number":["PATH"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["AI200088"],"award-info":[{"award-number":["AI200088"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["25PRE1372818"],"award-info":[{"award-number":["25PRE1372818"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["AI106699"],"award-info":[{"award-number":["AI106699"]}]},{"name":"NIH","award":["AI179103"],"award-info":[{"award-number":["AI179103"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The M protein of Group A\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    (GAS) is an essential virulence factor that promotes both superficial and invasive infections, as well as the development of immune sequela, including acute rheumatic fever and rheumatic heart disease. M protein is a prototypical sortase-anchored surface protein, yet has also been observed free of the GAS surface during human infection. This suggests a mechanism for its release, and this change in localization could influence innate immune detection, effector functions, and antigenic potential. Here, we show the protease SpeB cleaves M protein from the microbial surface, releasing a nearly full-length fragment that is highly resistant to any further degradation. Leveraging this insight to engineer strains where M protein either remains surface-locked or is constitutively secreted, we examine their separate contributions to disease. Only the secreted form of M protein drives inflammation in a mouse model of invasive infection, contributes to neutrophil activation and influx, a hallmark of these pyogenic infections. Furthermore, the release of M protein contributes to increased bacterial survival, suggesting the importance of maintenance of this mechanism within the species. This study thus highlights the potential relevance for proteolytic regulation of surface proteins in bacterial pathogenesis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014434","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T17:43:39Z","timestamp":1784137419000},"page":"e1014434","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic tethering of M protein drives pathological inflammation during group A Streptococcus infections"],"prefix":"10.1371","volume":"22","author":[{"given":"Ananya","family":"Dash","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris L.","family":"LaRock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa S.","family":"Varughese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Swaims-Kohlmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3035-5331","authenticated-orcid":true,"given":"Christopher N.","family":"LaRock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ppat.1014434.ref001","article-title":"Inflammasome\/IL-1\u03b2 Responses to Streptococcal Pathogens","author":"CN LaRock","year":"2015","journal-title":"Front 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