Niche exclusion of a lung pathogen in mice with designed probiotic communities

Abstract

For years, the airway microbiota have been theorized to be gatekeepers of respiratory health, as pathogens entering the airway make contact with resident microbes prior to or coincident with their interaction with host cells. Thus, modification of the native airway community may serve as a means of altering the local environment in favor of health. While probiotic supplementation to prevent pathogen infiltration has been explored extensively in the gut, little has been done to study this phenomenon in the lower respiratory tract. In this work, we hypothesize that synthetic bacterial communities introduced into the airway can serve as prophylactic countermeasures against infection by a model bacterial pathogen (Burkholderia thailandensis) in mice. We demonstrate that understanding of antagonistic interactions between a pathogen and airway microbiota in vitro can guide identification of probiotics with protective capabilities in vivo. While production of secondary metabolites appears to play a role in pathogen antagonism, exploitative competition appears to be the predominant mechanism by which the organisms studied here inhibit B. thailandensis. Specifically we show that niche overlap and resource competition between the probiotic and pathogen are predictive of probiotic performance in vivo. This work serves as a foundation for the rational design of probiotic communities for protection against and treatment of respiratory infections.