Intra-and interspecies communication in oral bacteria

口腔细菌的种内和种间通讯

• 批准号: 6984063
• 负责人: DONALD R DEMUTH
• 金额: $ 31.8万
• 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/6984063
• 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）：牙周病是由在牙龈袋中形成的复杂微生物群落中繁衍生息的细菌病原体引起的。这种细菌生物膜的启动和生长可能需要该群落中不同细菌物种之间复杂的分子通讯。最近有人提出，LuxS 基因产生的化学信号代表了一种广泛分布的种间通讯机制。 我们已经证明 LuxS 存在于牙周病原体（A. actinomycetemomitans 和 P. gingivalis）中，并且 LuxS 依赖性信号指导这些生物体中的特定种间反应。在此应用中，我们将确定各种口腔和非口腔生物之间 LuxS 依赖性通讯的范围和特异性、该信号通路调节 Aa 和 Pg 获取铁的机制以及信号在这些生物体毒力中所起的作用。我们将用来自其他口腔和非口腔生物体的信号和/或/luxS基因来补充Aa和Pg的LuxS缺陷菌株。我们还将确定 Aa 或 Pg 对同源和异源信号的反应是否不同。接下来，我们将检查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 吸收铁相关基因中所起的作用。 我们还表明，信号传导调节毒力相关基因的表达，因此将使用小鼠模型在体内确定信号传导对毒力的贡献。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。已鉴定出可能在信号转导中起作用的潜在候选蛋白；它们的基因将被灭活，并且将测试产生的细菌菌株对信号的反应。这些研究将提供一些初步证据，表明 LuxS 依赖性信号传导介导牙周病原体之间的种内和种间通讯。这反过来可能会导致新疗法的开发，通过阻断复杂细菌群落的通讯途径来控制其生长和发育。