IDENTIFICATION & REGULATION OF STRESS RESPONSE GENES IN PATHOGENIC STREPTOCOCCI

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 变形链球菌被认为是龋病的主要病原菌。变形链球菌也是感染性心内膜炎的重要病原体。这种微生物通过在牙齿表面形成不同的、多物种的生物膜来定植口腔，称为牙菌斑。这种病原体已经发展出多种机制来适应并在口腔恶劣的环境中茁壮成长。变形链球菌能够快速有效地对各种环境通量做出反应，包括严重的营养限制、pH和温度的波动以及氧化和渗透张力的变化。细菌暴露在这些不利的环境中，可以通过表达各种基因来诱导对各种环境挑战的交叉保护，从而诱导出一种应激耐受反应。逆境耐受基因受一组独特的转录调控因子的调控，包括交替的西格玛因子。然而，与其他病原体不同，变形链球菌和其他链球菌不编码任何替代的西格玛因子。另一方面，变形链球菌基因组中存在一些在其他细菌的应激反应中可能起作用的基因，但它们在胁迫和毒力中的作用尚未在变形链球菌中进行详细的研究。在这个项目中，我们计划识别有机体在恶劣的口腔环境中生存所必需的基因，以导致牙齿腐烂。成功完成我们的研究可能会导致开发新的治疗方法来预防龋齿。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Streptococcus mutans is considered as the major etiological agent in dental caries. S. mutans is also an important agent of infective endocarditis. The organism colonizes the oral cavity by forming diverse, multispecies biofilms on the tooth surface, known as dental plaque. This pathogen has developed multiple mechanisms to adapt and to flourish in the hostile environment of the oral cavity. S. mutans has the ability to respond rapidly and efficiently to various environmental fluxes, including severe nutrient limitation, fluctuations in pH and temperature, and changes in oxidative and osmotic tensions. Exposure of bacteria to these adverse environments can induce a stress tolerance response through expression of a wide variety of genes that provides cross-protection against diverse environmental challenges. Stress tolerance genes are regulated by unique groups of transcriptional regulators, including alternate sigma factors. However, unlike other pathogens, S. mutans and other streptococci do not encode any alternate sigma factors. On the other hand, some genes that putatively function in stress responses in other bacteria are present in the S. mutans genome, but their role in stress and virulence has not been investigated in S. mutans in great detail. In this project, we plan to identify genes that are necessary for the organism to survive in the hostile environment of the oral cavity to cause tooth decay. Successful completion of our studies may lead to the development of novel therapeutic treatments for the prevention of tooth decay.