{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:13:27Z","timestamp":1792858407828,"version":"4.5.0"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-1AI35060"],"award-info":[{"award-number":["R01-1AI35060"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35-GM118108"],"award-info":[{"award-number":["R35-GM118108"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Streptococcus pneumoniae<\/jats:italic> (the pneumococcus) is the major cause of bacterial pneumonia in the US and worldwide. Studies have shown that the differing chemical make-up between serotypes of its most important virulence factor, the capsule, can dictate disease severity. Here we demonstrate that control of capsule synthesis is also critical for infection and facilitated by two broadly conserved transcription factors, SpxR and CpsR, through a distal <jats:italic>cis<\/jats:italic>-regulatory element we name the <jats:italic>37-CE<\/jats:italic>. Strikingly, changing only three nucleotides within this sequence is sufficient to render pneumococcus avirulent. Using <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> approaches, we present a model where SpxR interacts as a unique trimeric quaternary structure with the <jats:italic>37-CE<\/jats:italic> to enable capsule repression in the airways. Considering its dramatic effect on infection, variation of the <jats:italic>37-CE<\/jats:italic> between serotypes suggests this molecular switch could be a critical contributing factor to this pathogen\u2019s serotype-specific disease outcomes.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011035","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T18:27:10Z","timestamp":1675189630000},"page":"e1011035","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Pneumococcal capsule expression is controlled through a conserved, distal cis-regulatory element during infection"],"prefix":"10.1371","volume":"19","author":[{"given":"David G.","family":"Glanville","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozcan","family":"Gazioglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Marra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie L.","family":"Tokars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Kushnir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhanie","family":"Habtom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Croucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaffa 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