Intra-and interspecies communication in oral bacteria

口腔细菌的种内和种间通讯

• 批准号: 6817414
• 负责人: DONALD R DEMUTH
• 金额: $ 33.56万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6817414
• 关键词: Actinobacillus actinomycetemcomitans; Bacteroides gingivalis; bacteria infection mechanism; bacterial DNA; bacterial genetics; biofilm; biological signal transduction; cell cell interaction; disease /disorder model; gene expression; genetic strain; heme; iron metabolism; laboratory mouse; microorganism culture; molecular cloning; nucleic acid sequence; oral bacteria; phosphotransferases; plasmids; polymerase chain reaction; protein structure function; site directed mutagenesis; species difference; transfection /expression vector; virulence

DESCRIPTION (provided by applicant): Periodontal disease is caused by bacterial pathogens that thrive in a complex microbial community, which forms in the gingival pocket. The initiation and growth of this bacterial biofilm likely requires sophisticated molecular communication among the bacterial various species in this community. A chemical signal produced by the LuxS gene has recently been suggested to represent a broadly distributed mechanism for interspecies communication. We have shown that LuxS is present in periodontal pathogens (A. actinomycetemomitans and P. gingivalis) and that the LuxS-dependent signal directs specific interspecies responses in these organisms. In this application, we will determine the range and specificity of LuxS-dependent communication among various oral and non-oral organisms, the mechanism by which this signaling pathway modulates iron acquisition by Aa and Pg and the role that signaling plays in the virulence of these organisms. We will complement LuxS-deficient strains of Aa and Pg with signals and/or/luxS genes from other oral and non-oral organisms. We will also determine if Aa or Pg respond differently to cognate and heterologous signals. Next, we will examine the growth of signal deficient strains in various iron sources and determine the role that LuxS dependent signaling plays in controlling genes involved in the uptake of iron by Pg and Aa. We have also shown that signaling regulates the expression of virulence-associated genes, thus the contribution of signaling to virulence will be determined in vivo using a mouse model. Finally, we will determine how signal information is transmitted within the bacterial cell to generate a specific response. Potential candidate proteins that may function in signal transduction have been identified; their genes will be inactivated and the resulting bacterial strains will be tested for their response to signal. These studies will provide some of the first evidence showing that LuxS-dependent signaling mediates intra- and interspecies communication among periodontal pathogens. This in turn may lead to the development of new therapeutics that may control growth and development of complex bacterial communities by blocking their communication pathways.

描述（由申请人提供）：牙周病是由细菌病原体引起的，这些细菌病原体在牙龈袋中形成的复杂微生物群落中茁壮成长。这种细菌生物膜的启动和生长可能需要该群落中细菌各种物种之间复杂的分子通讯。由LuxS基因产生的化学信号最近被认为代表了种间通讯的广泛分布机制。 我们已经证明LuxS存在于牙周病原体中（A.放线菌和牙龈卟啉单胞菌），并且LuxS依赖性信号指导这些生物体中的特定种间反应。在本申请中，我们将确定各种口腔和非口腔生物之间的LuxS依赖性通信的范围和特异性，该信号传导途径调节Aa和Pg铁获得的机制，以及信号传导在这些生物的毒力中发挥的作用。我们将用来自其他口腔和非口腔生物的信号和/或/luxS基因补充Aa和Pg的LuxS缺陷菌株。我们还将确定Aa或Pg是否对同源和异源信号有不同的反应。接下来，我们将研究信号缺陷菌株在各种铁源中的生长，并确定LuxS依赖性信号在控制Pg和Aa吸收铁的基因中所起的作用。 我们还表明，信号调节毒力相关基因的表达，因此信号对毒力的贡献将在体内使用小鼠模型确定。最后，我们将确定信号信息如何在细菌细胞内传递以产生特定的反应。可能在信号转导中起作用的潜在候选蛋白质已经被鉴定;它们的基因将被灭活，并且将测试所得细菌菌株对信号的响应。这些研究将提供一些第一个证据表明，LuxS依赖的信号介导牙周病原体之间的种内和种间通信。这反过来可能导致新疗法的开发，这些疗法可以通过阻断它们的通信途径来控制复杂细菌群落的生长和发育。