Genetic determinants of interbacterial competition during host colonization

项目摘要 微生物组的生物学功能对人类健康至关重要。这些扰动 微生物组可能导致破坏性后果，包括宿主发育不当， 增加对传染病的易感性。微生物之间的竞争相互作用 预计人口会影响微生物组的结构和功能，但 这些相互作用的分子机制仍然不清楚。理解 因此，微生物组动态对于预测和减轻生态失调和疾病风险至关重要 在人类身上。VI型分泌系统（T6SSs）是保守的蛋白质输出机制 在致病性和有益的人类相关细菌中都有发现。T6SS作为分子 注射器将毒性效应蛋白直接转运到竞争细胞中，导致抑制 或者死亡考虑到它们在细菌间竞争中的作用，T6SS能够构建 宿主相关生态位内的微生物群落。本提案的目的是 了解T6SS介导的相互作用如何塑造宿主相关的微生物组。结果 这项工作的一部分将有助于制定改善东道国健康的战略。最近的调查结果 使用鱿鱼光器官作为模型系统表明，细菌可以使用它们的T6SS， 竞争宿主中有限数量的定殖位点。拟议的工作将决定 T6SS介导的共定殖细菌杀伤的分子机制，以及 确定宿主中这些竞争性相互作用的空间和时间动态，以及 其对构建所得微生物组的影响。

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.