Although respiratory pathogens are a leading cause of death worldwide, we know very little about how invading bacterial pathogens overcome resident microbiota to colonize a host. Recently, we observed displacement of both culturable and unculturable bacteria from the upper respiratory tract upon infection with a common murine respiratory pathogen, Bordetella bronchiseptica. We examine the mechanistic basis for B. bronchiseptica displacement of other respiratory microbiota during infection. In parallel, we have demonstrated that resident microorganisms can prevent B. pertussis colonization and influence (apparent) host specificity. These results reveal an experimental system in which we can study how resident bacteria prevent pathogen invasion, and, provide rationale for manipulating microbiomes to protect the host and to create more accurate animal models of infectious diseases. Our approach has revealed complex intra-host competition between invading pathogen and resident microbiota and demonstrate novel effects of bacterial secretion systems and host immune functions in this in vivo competition. They also provide a striking example of displacement of chronic colonizers of the mammalian respiratory tract, potentially revealing novel pathways to disrupt the carrier state of a variety of common opportunistic respiratory pathogens.
