Genetic determinants of interbacterial competition during host colonization

Project Summary The biological functions of microbiomes are critical to human health. Perturbations of these microbiomes can lead to damaging consequences including improper host development and increased susceptibility to infectious disease. Competitive interactions among microbial populations are predicted to influence the structure and function of microbiomes, yet the molecular mechanisms underlying these interactions remain unclear. Understanding microbiome dynamics is therefore critical to predicting and mitigating dysbiosis and disease risk in humans. Type VI secretion systems (T6SSs) are a conserved protein export mechanism found in both pathogenic and beneficial human- associated bacteria. T6SSs act as molecular syringes to translocate toxic effector proteins directly into competitor cells, resulting in inhibition or death. Given their role in interbacterial competition, T6SSs are capable of structuring microbiome communities within a host-associated niche. The goal of this proposal is to understand how T6SS- mediated interactions shape host-associated microbiomes. The results of this work will facilitate the development of strategies to improve host health. Recent findings using the squid light organ as a model system indicate that bacteria can use their T6SS to compete for a limited number of colonization sites in the host. The proposed work will determine the molecular mechanisms underlying T6SS-mediated killing among co- colonizing bacteria, and determine the spatial and temporal dynamics of these competitive interactions in the host, and its effect on structuring the resulting microbiome.