Commensal colonization reduces burden and subsequent airway damage.

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