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Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> dominates the complex polymicrobial cystic fibrosis (CF) airway and is a leading cause of death in persons with CF. Interestingly, oral streptococcal colonization has been associated with stable CF lung function. The most abundant streptococcal species found in stable patients, <jats:italic>Streptococcus salivarius<\/jats:italic>, has been shown to downregulate pro-inflammatory cytokines in multiple colonization models. However, no studies have demonstrated how <jats:italic>S. salivarius<\/jats:italic> potentially improves lung function. Our lab previously demonstrated that the <jats:italic>P. aeruginosa<\/jats:italic> exopolysaccharide Psl promotes <jats:italic>S. salivarius<\/jats:italic> biofilm formation <jats:italic>in vitro<\/jats:italic>, suggesting a possible mechanism by which <jats:italic>S. salivarius<\/jats:italic> is incorporated into the CF airway microbial community. In this study, we demonstrate that co-infection of rats leads to enhanced <jats:italic>S. salivarius<\/jats:italic> colonization and reduced <jats:italic>P. aeruginosa<\/jats:italic> colonization. Histological scores for tissue inflammation and damage are lower in dual-infected rats compared to <jats:italic>P. aeruginosa<\/jats:italic> infected rats. Additionally, pro-inflammatory cytokines IL-1\u03b2, IL-6, CXCL2, and TNF-\u03b1 are downregulated during co-infection compared to <jats:italic>P. aeruginosa<\/jats:italic> single-infection. Lastly, RNA sequencing of cultures grown in synthetic CF sputum revealed that <jats:italic>P. aeruginosa<\/jats:italic> glucose metabolism genes are downregulated in the presence of <jats:italic>S. salivarius<\/jats:italic>, suggesting a potential alteration in <jats:italic>P. aeruginosa<\/jats:italic> fitness during co-culture. Overall, our data support a model in which <jats:italic>S. salivarius<\/jats:italic> colonization is promoted during co-infection with <jats:italic>P. aeruginosa<\/jats:italic>, whereas <jats:italic>P. aeruginosa<\/jats:italic> airway bacterial burden is reduced, leading to an attenuated host inflammatory response.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1144157","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T04:32:43Z","timestamp":1684989163000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Commensal colonization reduces Pseudomonas aeruginosa burden and subsequent airway damage"],"prefix":"10.3389","volume":"13","author":[{"given":"Sara N.","family":"Stoner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua J.","family":"Baty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Novak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Scoffield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"B21","doi-asserted-by":"publisher","first-page":"127298","DOI":"10.1016\/j.micres.2022.127298","article-title":"Pseudomonas aeruginosa behaviour in polymicrobial communities: the competitive and cooperative interactions conducting to the exacerbation of infections","volume":"268","author":"Al-Wrafy","year":"2023","journal-title":"Microbiol. 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