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