{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:23:01Z","timestamp":1780100581107,"version":"3.54.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011421","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000}}],"reference-count":101,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI155614"],"award-info":[{"award-number":["1R01AI155614"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI171038"],"award-info":[{"award-number":["1R01AI171038"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R56AI155614"],"award-info":[{"award-number":["1R56AI155614"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1U19AI158076"],"award-info":[{"award-number":["1U19AI158076"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1U01AI124302"],"award-info":[{"award-number":["1U01AI124302"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","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> is an opportunistic pathogen that colonizes the upper respiratory tract asymptomatically and, upon invasion, can lead to severe diseases including otitis media, sinusitis, meningitis, bacteremia, and pneumonia. One of the first lines of defense against pneumococcal invasive disease is inflammation, including the recruitment of neutrophils to the site of infection. The invasive pneumococcus can be cleared through the action of serine proteases generated by neutrophils. It is less clear how serine proteases impact non-invasive pneumococcal colonization, which is the key first step to invasion and transmission. One significant aspect of pneumococcal biology and adaptation in the respiratory tract is its natural competence, which is triggered by a small peptide CSP. In this study, we investigate if serine proteases are capable of degrading CSP and the impact this has on pneumococcal competence. We found that CSP has several potential sites for trypsin-like serine protease degradation and that there were preferential cleavage sites recognized by the proteases. Digestion of CSP with two different trypsin-like serine proteases dramatically reduced competence in a dose-dependent manner. Incubation of CSP with mouse lung homogenate also reduced recombination frequency of the pneumococcus. These <jats:italic>ex vivo<\/jats:italic> experiments suggested that serine proteases in the lower respiratory tract reduce pneumococcal competence. This was subsequently confirmed measuring <jats:italic>in vivo<\/jats:italic> recombination frequencies after induction of protease production via poly (I:C) stimulation and via co-infection with influenza A virus, which dramatically lowered recombination events. These data shed light on a new mechanism by which the host can modulate pneumococcal behavior and genetic exchange via direct degradation of the competence signaling peptide.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011421","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T18:09:14Z","timestamp":1685556554000},"page":"e1011421","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Airway proteolytic control of pneumococcal competence"],"prefix":"10.1371","volume":"19","author":[{"given":"Haley","family":"Echlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Iverson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Sardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1798-1760","authenticated-orcid":true,"given":"Jason W.","family":"Rosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"issue":"7","key":"ppat.1011421.ref001","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a010215","article-title":"The pneumococcus: epidemiology, microbiology, and pathogenesis.","volume":"3","author":"B Henriques-Normark","year":"2013","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"6","key":"ppat.1011421.ref002","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41579-018-0001-8","article-title":"Streptococcus pneumoniae: transmission, colonization and invasion","volume":"16","author":"JN Weiser","year":"2018","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"ppat.1011421.ref003","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S1473-3099(04)00938-7","article-title":"Streptococcus pneumoniae colonisation: the key to pneumococcal disease","volume":"4","author":"D Bogaert","year":"2004","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"ppat.1011421.ref004","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.yexcr.2010.03.003","article-title":"Commensal pathogens, with a focus on Streptococcus pneumoniae, and interactions with the human host","volume":"316","author":"B Henriques-Normark","year":"2010","journal-title":"Exp Cell Res"},{"issue":"2","key":"ppat.1011421.ref005","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.GPP3-0004-2018","article-title":"Streptococcus pneumoniae: Invasion and Inflammation.","volume":"7","author":"AJ Loughran","year":"2019","journal-title":"Microbiol Spectr"},{"issue":"3","key":"ppat.1011421.ref006","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1086\/322021","article-title":"Microbiological and inflammatory factors associated with the development of pneumococcal pneumonia","volume":"184","author":"F Dallaire","year":"2001","journal-title":"J Infect Dis"},{"issue":"4","key":"ppat.1011421.ref007","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.4049\/jimmunol.0900688","article-title":"Human neutrophils kill Streptococcus pneumoniae via serine proteases","volume":"183","author":"AJ Standish","year":"2009","journal-title":"J Immunol"},{"issue":"7","key":"ppat.1011421.ref008","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nri1841","article-title":"Neutrophil serine proteases: specific regulators of inflammation","volume":"6","author":"CT Pham","year":"2006","journal-title":"Nat Rev Immunol"},{"issue":"5","key":"ppat.1011421.ref009","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/iub.186","article-title":"Serine proteases","volume":"61","author":"E. 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