Swarming as a model for surface-sensing in Salmonella typhimurium

描述（由申请人提供）：群体是鞭毛细菌在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）具有相同的特征，因此是揭示和理解细菌表面感知机制的一个特别相关的模型。蜂拥细胞通常产生更多的鞭毛，并分泌表面活性剂和多糖，通过产生水分和提供润滑来帮助表面运动。我们在这个资助期的研究已经确定，外部湿度对鼠伤寒沙门氏菌的群集比增加鞭毛的产量更重要。对趋化信号通路中群居缺陷突变体的研究已经导致了令人惊讶的发现，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，在这个模型中，关于环境有多湿（以及如何有利于蜂群）的信息被传递到鞭毛III型分泌系统，以控制控制鞭毛生物合成中最后一个也是能量上最昂贵的步骤的负规则的输出。鞭毛马达的开关与产生湿气有关。有趣的是，“湿润”信号通过鞭毛系统传递到SPI-1毒力系统，该系统指定负责向宿主细胞注射毒力因子的针状结构。我们还发现，fliL的功能一直是个谜，它只对表面运动至关重要；fliL是鞭毛操纵子中第一个专门合成开关和III型输出复合体的基因。我们在趋化系统中发现了三个新的参与者，它们似乎共同促进了表面殖民化。提出的工作旨在了解(1)鞭毛产生和感知湿度的机制，(2)FliL在表面运动中的作用，(3)连接运动和毒力系统的调节回路，以及(4)三种新的趋化基因之间的新功能关联。我们的研究有望导致对各种细菌表面运动调节的统一理解，以及控制鞭毛成分和毒力因子分泌的共同原理，这两者都是由表面接触调节的。公共卫生相关性：群体是鞭毛细菌在地表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）具有相同的特征，因此是揭示和理解细菌表面感知机制的一个特别相关的模型。我们的研究预计将导致对各种细菌物种表面运动调节的统一理解，阐明控制鞭毛成分和毒力因子通过针状复合物输出的分泌的共同原理，并揭示这些纳米机器测量外部含水量的新机制。

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.