Publications

Reconfiguration of the Respiratory Tract Microbiome to Prevent and Treat Burkholderia Infection

Branda, Steven B.; Collette, Nicole C.; Aiosa, Nicole A.; Garg, Neha G.; Mageeney, Catherine M.; Williams, Kelly P.; Phillips, Ashlee P.; Hern, Kelsey H.; Arkin, Adam A.; Ricken, James B.; Wilde, Delaney W.; Dogra, Sahiba D.; Humphrey, Brittany M.; Poorey, Kunal N.; Courtney, Colleen C.

New approaches to preventing and treating infections, particularly of the respiratory tract, are needed. One promising strategy is to reconfigure microbial communities (microbiomes) within the host to improve defense against pathogens. Probiotics and prebiotics for gastrointestinal (GI) infections offer a template for success. We sought to develop comparable countermeasures for respiratory infections. First, we characterized interactions between the airway microbiome and a biodefense-related respiratory pathogen ( Burkholderia thailandensis ; Bt), using a mouse model of infection. Then, we recovered microbiome constituents from the airway and assessed their ability to re-colonize the airway and protect against respiratory Bt infection. We found that microbiome constituents belonging to Bacillus and related genuses frequently displayed colonization and anti-Bt activity. Comparative growth requirement profiling of these Bacillus strains vs Bt enabled identification of candidate prebiotics. This work serves as proof of concept for airway probiotics, as well as a strong foundation for development of airway prebiotics.