Three Distinct Contact-Dependent Growth Inhibition Systems Mediate Interbacterial Competition by the Cystic Fibrosis Pathogen Burkholderia dolosa.

The respiratory tracts of individuals afflicted with cystic fibrosis (CF) harbor complex polymicrobial communities. By an unknown mechanism, species of the Gram-negative complex, such as , can displace other bacteria in the CF lung, causing cepacia syndrome, which has a poor prognosis. The genome of strain AU0158 (AU0158) contains three loci that are predicted to encode contact-dependent growth inhibition (CDI) systems. CDI systems function by translocating the toxic C terminus of a large exoprotein directly into target cells, resulting in growth inhibition or death unless the target cells produce a cognate immunity protein. We demonstrate here that each of the three loci in AU0158 encodes a distinct CDI system that mediates interbacterial competition in an allele-specific manner. While only two of the three loci were expressed under the conditions tested, the third conferred immunity under these conditions due to the presence of an internal promoter driving expression of the gene. One AU0158 allele is highly similar to in strain E264 (E264), and we showed that their BcpI proteins are functionally interchangeable, but contact-dependent signaling (CDS) phenotypes were not observed in AU0158. Our findings suggest that the CDI systems of AU0158 may provide this pathogen an ecological advantage during polymicrobial infections of the CF respiratory tract. Human-associated polymicrobial communities can promote health and disease, and interbacterial interactions influence the microbial ecology of such communities. Polymicrobial infections of the cystic fibrosis respiratory tract impair lung function and lead to the death of individuals suffering from this disorder; therefore, a greater understanding of these microbial communities is necessary for improving treatment strategies. Bacteria utilize contact-dependent growth inhibition systems to kill neighboring competitors and maintain their niche within multicellular communities. Several cystic fibrosis pathogens have the potential to gain an ecological advantage during infection via contact-dependent growth inhibition systems, including Our research is significant, as it has identified three functional contact-dependent growth inhibition systems in that may provide this pathogen a competitive advantage during polymicrobial infections.