AUTHOR=Stoner Sara N. , Baty Joshua J. , Novak Lea , Scoffield Jessica A. 

TITLE=Commensal colonization reduces Pseudomonas aeruginosa burden and subsequent airway damage

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1144157

DOI=10.3389/fcimb.2023.1144157

ISSN=2235-2988

ABSTRACT=<p><italic>Pseudomonas aeruginosa</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, <italic>Streptococcus salivarius</italic>, has been shown to downregulate pro-inflammatory cytokines in multiple colonization models. However, no studies have demonstrated how <italic>S. salivarius</italic> potentially improves lung function. Our lab previously demonstrated that the <italic>P. aeruginosa</italic> exopolysaccharide Psl promotes <italic>S. salivarius</italic> biofilm formation <italic>in vitro</italic>, suggesting a possible mechanism by which <italic>S. salivarius</italic> is incorporated into the CF airway microbial community. In this study, we demonstrate that co-infection of rats leads to enhanced <italic>S. salivarius</italic> colonization and reduced <italic>P. aeruginosa</italic> colonization. Histological scores for tissue inflammation and damage are lower in dual-infected rats compared to <italic>P. aeruginosa</italic> infected rats. Additionally, pro-inflammatory cytokines IL-1β, IL-6, CXCL2, and TNF-α are downregulated during co-infection compared to <italic>P. aeruginosa</italic> single-infection. Lastly, RNA sequencing of cultures grown in synthetic CF sputum revealed that <italic>P. aeruginosa</italic> glucose metabolism genes are downregulated in the presence of <italic>S. salivarius</italic>, suggesting a potential alteration in <italic>P. aeruginosa</italic> fitness during co-culture. Overall, our data support a model in which <italic>S. salivarius</italic> colonization is promoted during co-infection with <italic>P. aeruginosa</italic>, whereas <italic>P. aeruginosa</italic> airway bacterial burden is reduced, leading to an attenuated host inflammatory response.</p>