Airway Corynebacterium interfere with Streptococcus pneumoniae and Staphylococcus aureus 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 Corynebacterium, 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 Streptococcus pneumoniae and Staphylococcus aureus. In this study, Corynebacterium-mediated protective effects against S. pneumoniae and S. aureus were directly compared using in vivo and in vitro models. Pre-exposure to Corynebacterium pseudodiphtheriticum reduced the ability of S. aureus and S. pneumoniae 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. pseudodiphtheriticum or Corynebacterium accolens, and this effect was dependent on live Corynebacterium colonizing the epithelial cells. However, Corynebacterium-secreted factors had distinct effects on each pathogen. Corynebacterium lipase activity was bactericidal against S. pneumoniae, but not S. aureus. Instead, the hemolytic activity of pore-forming toxins produced by S. aureus was directly blocked by a novel Corynebacterium-secreted factor with protease activity. Taken together, these results suggest diverse mechanisms by which Corynebacterium contribute to the protective effect of the airway microbiome against opportunistic bacterial pathogens.