Intra-and interspecies communication in oral bacteria

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。这种细菌生物膜的形成和生长可能需要在这个群落中不同种类的细菌之间进行复杂的分子交流。LuxS基因产生的一种化学信号最近被认为代表了一种广泛分布的物种间交流机制。我们已经证明LuxS存在于牙周病原体（放线菌和牙龈卟啉单胞菌）中，并且LuxS依赖的信号指导这些生物的特定种间反应。在本应用中，我们将确定各种口服和非口服生物之间luxs依赖性通信的范围和特异性，该信号通路调节Aa和Pg获取铁的机制以及该信号通路在这些生物的毒力中所起的作用。我们将用其他口腔和非口腔生物的信号和/或/luxS基因来补充Aa和Pg缺乏luxS的菌株。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，我们将研究信号缺乏菌株在不同铁源下的生长情况，并确定LuxS依赖性信号在控制Pg和Aa摄取铁的基因中所起的作用。我们还表明，信号传导调节毒力相关基因的表达，因此，信号传导对毒力的贡献将通过小鼠模型在体内确定。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。已经确定了可能在信号转导中起作用的潜在候选蛋白；他们的基因将被灭活，由此产生的细菌菌株将被测试对信号的反应。这些研究将提供一些第一个证据，表明luxs依赖性信号介导牙周病原体之间的种内和种间交流。这反过来可能导致新疗法的发展，这些疗法可能通过阻断复杂细菌群落的通讯途径来控制它们的生长和发育。

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.