Airway interfere with and infection and express secreted factors selectively targeting each pathogen.

The composition of the respiratory tract microbiome is a notable predictor of infection-related morbidities and mortalities among both adults and children. Species of which are largely present as commensals in the upper airway and other body sites, are associated with lower colonization rates of opportunistic bacterial pathogens such as and . In this study, -mediated protective effects against and were directly compared using and models. Pre-exposure to reduced the ability of and to infect the lungs of mice, indicating a broadly protective effect. Adherence of both pathogens to human respiratory tract epithelial cells was significantly impaired following pre-exposure to C. or , and this effect was dependent on live colonizing the epithelial cells. However, -secreted factors had distinct effects on each pathogen. lipase activity was bactericidal against , but not . Instead, the hemolytic activity of pore-forming toxins produced by was directly blocked by a novel -secreted factor with protease activity. Taken together, these results suggest diverse mechanisms by which contribute to the protective effect of the airway microbiome against opportunistic bacterial pathogens.