Genetic determinants of interbacterial competition during host colonization

宿主定殖过程中细菌间竞争的遗传决定因素

• 批准号: 10206201
• 负责人: Alecia Septer
• 金额: $ 36.58万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10206201
• 关键词: Bacteria; Biological Models; Biological Process; Cells; Cessation of life; Communicable Diseases; Communities; Development; Genetic Determinism; Goals; Health; Human; Lead; Light; Mediating; Molecular; Organ; Pathogenicity; Population; Predisposition; Protein Export Pathway; Proteins; Role; Shapes; Site; Squid; Structure; Syringes; System; Work; cell killing; disorder risk; dysbiosis; host colonization; improved; member; microbial; microbiome; microbiome alteration; Bacteria; Biological Models; Biological Process; Cells; Cessation of life; Communicable Diseases; Communities; Development; Genetic Determinism; Goals; Health; Human; Lead; Light; Mediating; Molecular; Organ; Pathogenicity; Population; Predisposition; Protein Export Pathway; Proteins; Role; Shapes; Site; Squid; Structure; Syringes; System; Work; cell killing; disorder risk; dysbiosis; host colonization; improved; member; microbial; microbiome; microbiome alteration

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.

项目摘要 微生物组的生物学功能对人类健康至关重要。这些的扰动 微生物组可能会导致破坏性后果，包括宿主发展不当和 增加对传染病的敏感性。微生物之间的竞争相互作用 预计种群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尚不清楚。理解 因此，微生物组动力学对于预测和减轻营养不良和疾病风险至关重要 在人类中。 VI型分泌系统（T6SS）是保守的蛋白质导出机制 在病原和有益的人类相关细菌中发现。 T6SS充当分子 注射器将有毒效应蛋白直接转移到竞争细胞中，从而抑制 或死亡。鉴于它们在细菌间竞争中的作用，T6SS能够构建 与宿主相关的利基市场中的微生物组社区。该提议的目的是 了解T6SS介导的相互作用如何形成与宿主相关的微生物组。结果 这项工作将有助于制定改善宿主健康的战略。最新发现 使用鱿鱼光器官作为模型系统，表明细菌可以使用其T6SS 争夺宿主中有限数量的殖民地地点。拟议的工作将决定 T6SS介导的共殖化细菌中杀死的分子机制，以及 确定这些竞争相互作用在主机中的空间和时间动态，以及 它对结构产生的微生物组的影响。