Genetic determinants of interbacterial competition during host colonization

项目摘要 微生物群的生物学功能对人类健康至关重要。它们的微扰 微生物群可导致破坏性后果，包括宿主发育不当和 对传染病的易感性增加。微生物间的竞争性相互作用 据预测，种群会影响微生物群落的结构和功能，然而 这些相互作用背后的分子机制尚不清楚。理解 因此，微生物组动力学对于预测和缓解生态失调和疾病风险至关重要。 在人类身上。VI型分泌系统(T6SS)是一种保守的蛋白质输出机制 在致病和有益的人类相关细菌中都有发现。T6SS作为分子的作用 注射器将有毒的效应蛋白直接转移到竞争细胞中，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 寄主相关生态位内的微生物群落。这项提议的目标是 了解T6SS介导的相互作用如何塑造宿主相关的微生物群。结果是 这项工作的进展将有助于制定改善宿主健康的战略。最新发现 以鱿鱼光器官为模型系统表明，细菌可以利用它们的T6SS来 在宿主中争夺有限数量的殖民地点。拟议的工作将确定 T6SS介导的共生细菌之间杀伤的分子机制，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 它对由此产生的微生物群结构的影响。

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.