Global regulation of toxin production in Clostridium perfringens

该项目涉及调查导致致命伤口感染的细菌如何控制作为疾病过程基本要素的有毒蛋白质的产生。在所有致病菌中，都有特定的基因编码与疾病有关的毒力因子。这些基因的表达通常由称为调节基因的其他基因的产物控制。这些调节网络的功能通常对环境刺激做出反应。该项目涉及一个监管网络的详细功能分析，该网络首先在本实验室中被确定，并控制与气性坏疽有关的细胞外毒素的表达。该项目的总体目标是详细了解这一监管过程所涉及的机制。具体而言，该项目旨在确定与环境信号相互作用或与编码细菌毒素的基因结合的调节蛋白的功能组分，以确定调节蛋白结合的靶位点的性质，并检查存在另一个参与此过程的调节基因的假设。该项目将对我们了解入侵细菌和宿主组织之间发生的复杂相互作用做出重大贡献。如果我们要充分理解细菌如何引起疾病，那么我们必须了解细菌如何控制作为疾病过程组成部分的有毒产物的产生。

This project involves an investigation of how the bacteria that cause an often fatal wound infection control the production of the toxic proteins that are essential elements of the disease process. In all pathogenic bacteria there are specific genes that encode the virulence factors that are involved in the disease. The expression of these genes is generally controlled by the products of other genes known as regulatory genes. The function of these regulatory networks is generally responsive to environmental stimuli. This project involves the detailed functional analysis of a regulatory network that was first identified in this laboratory and which controls the expression of extracellular toxins that have been implicated in gas gangrene. The overall objectives of the project are to develop a detailed understanding of the mechanisms involved in this regulatory process. Specifically, the project aims to determine the functional components of the regulatory proteins that interact with the environmental signal or which bind to the genes encoding the bacterial toxins, to determine the nature of the target sites to which the regulatory proteins bind, and to examine the hypothesis that there is another regulatory gene that is involved in this process. The project will make a major contribution to our knowledge of the complex interactions that occur between an invading bacterium and the host tissues. If we are to fully comprehend how bacteria cause disease then it is critical that we understand how bacteria control the production of the toxic products that are an integral part of the disease process.