Swarming as a model for surface-sensing in Salmonella typhimurium

描述（由申请方提供）：群集是鞭毛细菌表面定植的一种普遍模式。它与其他表面现象如生物膜形成和宿主入侵具有共同特征，因此是揭示和理解细菌表面传感机制的特别相关的模型。蜂群细胞通常制造更多的鞭毛，并分泌表面活性剂和多糖，通过产生湿润和提供润滑来帮助表面运动。我们在本研究期间的研究已经证实，外部湿度对南半球的蜂群形成更为关键。鼠伤寒沙门氏菌比鞭毛的生产增加。对趋化性信号通路中的群集缺陷突变体的研究已经导致了令人惊讶的发现，即鞭毛本身参与产生和感知湿度以控制其自身的生物发生和运动。我们的数据支持一个模型，在该模型中，关于环境如何潮湿（因此如何有利于群集）的信息被传递到鞭毛III型分泌系统，以控制出口的负经常控制鞭毛生物合成中的最后一步，也是最昂贵的步骤。鞭毛马达的切换与产生湿度有关。有趣的是，“湿度”信号通过鞭毛系统传递到SPI-1毒力系统，该系统指定负责将毒力因子注入宿主细胞的Needle结构。我们还发现，fliL，其功能一直是一个谜，是必不可少的表面运动; fliL是第一个基因在鞭毛操纵子致力于合成开关和III型出口复合物。我们发现了趋化系统中的三个新参与者，它们似乎共同促进表面殖民化。拟议的工作旨在了解（1）鞭毛产生和感觉湿度的机制，（2）FliL在表面运动中的作用，（3）连接运动和毒性系统的调节回路，以及（4）三个新趋化性基因之间的新功能关联。我们的研究预计将导致一个统一的理解，在各种细菌物种的表面运动的调节，以及共同的原则，管理鞭毛成分和毒力因子的分泌，这两者都是由表面接触调节。公共卫生相关性：群集是一种普遍存在的鞭毛细菌表面定植模式。它与其他表面现象如生物膜形成和宿主入侵具有共同特征，因此是揭示和理解细菌表面传感机制的特别相关的模型。我们的研究预计将导致对各种细菌物种表面运动性调节的统一理解，阐明控制通过针复合体输出的鞭毛成分和毒力因子分泌的共同原则，并揭示新的机制通过这些纳米机器测量外部含水量。

DESCRIPTION (provided by applicant): Swarming is a widespread mode of surface colonization by flagellated bacteria. It shares features with other surface phenomenon such as biofilm formation and host invasion, and is therefore a particularly relevant model for uncovering and understanding bacterial surface-sensing mechanisms. Swarmer cells generally make more flagella, and excrete surfactants and polysaccharides that aid surface motility by generating wetness and providing lubrication. Our studies in this grant period have established that external wetness is more critical for swarming in S. typhimurium than increased production of flagella. Studies with swarming-defective mutants in the chemotaxis signaling pathway have led to the surprising discovery that the flagellum itself is involved in both generating and sensing wetness to control its own biogenesis and movement. Our data support a model in which information about how wet the environment is (and hence how conducive to swarming) is conveyed to the flagellar Type III secretion system to control export of a negative regular that controls the last and energetically most costly step in flagellar biosynthesis. Switching of the flagellar motor is implicated in generating wetness. Interestingly, the 'wetness' signal is conveyed via the flagellar system to the SPI-1 virulence system, which specifies the Needle structure responsible for injecting virulence factors into host cells. We have also discovered that fliL, whose function has been a mystery, is essential only for surface motility; fliL is the first gene in a flagellar operon dedicated to synthesis of the switch and the Type III export complex. We have uncovered three new players in the chemotaxis system that appear to work together to promote surface colonization. The proposed work aims to understand (1) the mechanism by which the flagellum generates and senses wetness, (2) the role of FliL in surface motility, (3) the regulatory circuits that connect the motility and virulence systems, as well as (4) the novel functional association between the three new chemotaxis genes. Our studies are expected to lead to a unified understanding of the regulation of surface motility in a variety of bacterial species, as well as common principles that govern the secretion of flagellar components and virulence factors, both of which are regulated by surface contact. PUBLIC HEALTH RELEVANCE: Swarming is a widespread mode of surface colonization by flagellated bacteria. It shares features with other surface phenomenon such as biofilm formation and host invasion, and is therefore a particularly relevant model for uncovering and understanding bacterial surface-sensing mechanisms. Our studies are expected to lead to a unified understanding of the regulation of surface motility in a variety of bacterial species, to an elucidation of common principles that govern the secretion of flagellar components and virulence factors exported through the Needle complex, and to uncovering new mechanisms by which external water content is gauged by these nanomachines.