Fimbrial expression in Salmonella: regulation and coordination

描述（由申请人提供）：S。肠型鼠伤寒是一种重要的人类病原体，在进食受污染的食物后会引致急性肠胃炎。人类感染的主要媒介之一是受污染的家禽，因为细菌很容易感染这些动物。在两种宿主（人和鸡）中，病原体在胃肠道（GI）中定殖和生长。关于在这种环境中细菌存活的微生物学知之甚少，本提案的目的之一是研究人类和鸡的肠上皮细胞上的细菌生长。我们已经表明，一种蛋白质，FimZ，在调节参与宿主/病原体相互作用的几种表型的表达中起着至关重要的作用。这种蛋白质影响细菌移动、粘附和侵入真核细胞的能力。这些事件中的每一个都是有效的殖民和增长所必需的。我们建议阐明FimZ产生的机制及其与其他蛋白质相互作用的能力。这些将是重要的相互作用，因为它们将决定主要细菌粘附蛋白之一的功能水平和程度。为了实现这些目标，我们建议使用的技术，这将使我们能够调查的分子病原体的saltophilia生物。鼠伤寒血清型在上皮表面上定殖和生长的能力是细菌表面上粘附因子产生的函数。这些因子通常是分离的附属物，称为菌毛或皮利，使细菌能够识别真核细胞表面的受体。FimZ是一种调节这些粘附因子之一表达的蛋白质，我们的初步证据表明，在鼠伤寒血清型中菌毛表达之间存在协调相互作用。这些细菌有可能产生许多不同类型的菌毛。目前尚不清楚细菌如何协调和整合多种菌毛类型的表达。在这个建议中，我们描述了实验，启动研究协调菌毛基因的表达。这将是对鼠伤寒血清型中的全局菌毛表达的首次系统研究，并将开始解决有关这些细菌以程序化和调节的方式非随机产生粘附素的能力的问题。由于许多病原菌具有产生多种菌毛类型的潜力，这些研究对许多种病原菌也具有意义。公共卫生相关性：这些研究调查了沙门氏菌粘附因子的协调调节和作用。这些因子在促进作为感染的第一阶段的对宿主细胞的附着方面是重要的。

DESCRIPTION (provided by applicant): S. enterica serovar Typhimurium is an important human pathogen causing acute gastroenteritis following ingestion of contaminated food. One of the major vehicles of infection for humans is contaminated poultry because the bacteria easily infect these animals. In both hosts, humans and chickens, the pathogen colonizes and grows in the gastrointestinal (GI) tract. Very little is known about the microbiology of bacterial survival in this environment and one of the aims of this proposal is to investigate bacterial growth on intestinal epithelia of both humans and chickens. We have shown that a protein, FimZ, plays a crucial role in regulating the expression of several phenotypes that are involved in the host/pathogen interaction. This protein influences the ability of bacteria to move, adhere to, and invade eucaryotic cells. Each of these events is necessary for efficient colonization and growth. We propose to elucidate the mechanisms by which FimZ is produced and its ability to interact with other proteins. These will be important interactions since they will determine the level and degree of function of one of the major bacterial adherence proteins. In order to achieve these goals we propose to use techniques that will enable us to investigate the molecular pathogenies of salmonella organisms. The ability of serovar Typhimurium to colonize and grow on epithelial surfaces is a function of the production of adherence factors on the surface of the bacteria. These factors are frequently discrete appendages, named fimbriae or pili, that allow the bacteria to recognize receptors on eucaryotic cell surfaces. FimZ is a protein that regulates the expression of one of these adherence factors and our preliminary evidence indicates that there is coordinate interaction between fimbrial expression in serovar Typhimurium. These bacteria have the potential to produce numerous different types of fimbriae. It is currently unknown how the bacteria coordinate and integrate the expression of multiple fimbrial types. In this proposal we describe experiments to initiate studies on coordinate fimbrial gene expression. These will be the first systematic investigations of global fimbrial expression in serovar Typhimurium and will begin to address questions about the ability of these bacteria to non-stochastically produce adhesins in a programmed and regulated fashion. Since many pathogenic bacteria have the potential to produce multiple fimbrial types, these studies will also have significance for many species of pathogenic bacteria. PUBLIC HEALTH RELEVANCE: These studies investigate the coordinate regulation and role of Salmonella adherence factors. These factors are important in facilitating attachment to host cells as a first stage of infection.