from the Human Nose Inhibit Colonization with a Secreted Peptidoglycan Endopeptidase

Moraxella catarrhalis is found almost exclusively within the human respiratory tract. This pathobiont is associated with ear infections and the development of respiratory illnesses, including allergies and asthma. Given the limited ecological distribution of M. catarrhalis, we hypothesized that we could leverage the nasal microbiomes of healthy children without M. catarrhalis to identify bacteria that may represent potential sources of therapeutics. was more abundant in the noses of healthy children compared to children with cold symptoms and M. catarrhalis. We cultured from nasal samples and determined that most isolates of Rothia dentocariosa and "Rothia similmucilaginosa" were able to fully inhibit the growth of M. catarrhalis , whereas isolates of Rothia aeria varied in their ability to inhibit M. catarrhalis. Using comparative genomics and proteomics, we identified a putative peptidoglycan hydrolase called ecreted ntien (SagA). This protein was present at higher relative abundance in the secreted proteomes of and than in those from non-inhibitory , suggesting that it may be involved in M. catarrhalis inhibition. We produced SagA from in Escherichia coli and confirmed its ability to degrade M. catarrhalis peptidoglycan and inhibit its growth. We then demonstrated that and reduced M. catarrhalis levels in an air-liquid interface culture model of the respiratory epithelium. Together, our results suggest that restricts M. catarrhalis colonization of the human respiratory tract . Moraxella catarrhalis is a pathobiont of the respiratory tract, responsible for ear infections in children and wheezing illnesses in children and adults with chronic respiratory diseases. Detection of M. catarrhalis during wheezing episodes in early life is associated with the development of persistent asthma. There are currently no effective vaccines for M. catarrhalis, and most clinical isolates are resistant to the commonly prescribed antibiotics amoxicillin and penicillin. Given the limited niche of M. catarrhalis, we hypothesized that other nasal bacteria have evolved mechanisms to compete against M. catarrhalis. We found that are associated with the nasal microbiomes of healthy children without Next, we demonstrated that inhibit M. catarrhalis and on airway cells. We identified an enzyme produced by called SagA that degrades M. catarrhalis peptidoglycan and inhibits its growth. We suggest that or SagA could be developed as highly specific therapeutics against M. catarrhalis.