Swarming as a model for surface-sensing in Salmonella typhimurium

集群作为鼠伤寒沙门氏菌表面传感模型

• 批准号: 7678937
• 负责人: Rasika M Harshey
• 金额: $ 28.72万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7678937
• 关键词: Agar; Anabolism; Back; Bacteria; Behavior; Binding Sites; Biogenesis; Biological Assay; C-terminal; Cells; Chemoreceptors; Chemotaxis; Complex; Data; Desiccation; Environment; Filament; Flagella; Foundations; Genes; Grant; Lead; Lubrication; Mastigophora; Methods; Methylation; Microbial Biofilms; Modeling; Molecular Genetics; Motor; Movement; Needles; Operon; Organism; Pathway interactions; Polysaccharides; Production; Property; Proteins; Protons; Publishing; Regulation; Research Design; Rest; Role; Salmonella typhimurium; Sensory; Signal Pathway; Signal Transduction; Specific qualifier value; Structure; Surface; System; Testing; Time; Type III Secretion System Pathway; Virulence; Virulence Factors; Water; Work; base; cell motility; feeding; genetic analysis; kinetosome; lambda Spi-1; mutant; nanomachine; novel; public health relevance; receptor; research study; response; sensor; sugar; surfactant

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.

描述（由申请人提供）：集群是有鞭毛细菌的一种广泛的表面定殖模式。它与其他表面现象（例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传感机制的特别相关的模型。集群细胞通常会产生更多的鞭毛，并分泌表面活性剂和多糖，通过产生湿度和提供润滑来帮助表面运动。我们在本资助期间的研究已经证实，外部湿度对于鼠伤寒沙门氏菌的集群影响比鞭毛产量的增加更为重要。对趋化信号通路中群体缺陷突变体的研究得出了令人惊讶的发现，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，其中有关环境湿度（以及因此如何有利于蜂群）的信息被传送到鞭毛III型分泌系统，以控制负常规的输出，该负常规控制鞭毛生物合成中最后且能量最昂贵的步骤。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针结构。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用于合成开关和 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，它们似乎共同努力促进表面定植。拟议的工作旨在了解（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）三个新趋化基因之间的新功能关联。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，以及控制鞭毛成分和毒力因子分泌的共同原理，这两者都受到表面接触的调节。公共卫生相关性：集群是有鞭毛细菌在表面定植的一种广泛模式。它与其他表面现象（例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调节的统一理解，阐明控制鞭毛成分和通过针复合体输出的毒力因子的分泌的共同原理，并揭示这些纳米机器测量外部水含量的新机制。