Molecular Analyses of the Competence Regulatory Network in Streptococcus mutans

遗传转化能力的发展是细菌能够从其环境中吸收DNA的手段。通过这种方式，细菌迅速获得新的基因或特性，使它们能够在恶劣的环境中生存，使它们对抗生素产生抗药性，或变得更具毒性（能够引起疾病）。通过转化外源DNA的结合使细菌获得遗传变异，这是推动细菌进化的主要力量。此外，通过遗传转化将基因构建的DNA引入细菌菌株是分子克隆和其他细菌遗传操作中广泛使用的方法。众所周知，许多细菌具有遗传转化的能力。然而，当细菌发展出吸收DNA的能力以及这一过程是如何被调节的，人们还没有完全了解。在一种被称为链球菌的细菌群中，它倾向于生活在人类和动物身上，能力已知是由两个信号系统之一，ComCDE和ComRS调节的。有趣的是，变形链球菌作为牙菌斑的常驻成员，同时拥有ComCDE和ComRS系统，这两个系统被证明可以调节遗传能力。我们实验室和其他人最近的工作进一步表明，变形链球菌和其他相关物种的能力发展在多个水平上受到调控，涉及一个复杂的调控网络和信号转导途径之间的多个交叉连接。然而，这种复杂调控网络的分子细节尚未完全阐明。拟议的研究旨在解开变形链球菌中这个复杂的调控网络。本研究结果将极大地促进我们对细菌如何调节其遗传可塑性，抵抗抗生素和适应不断变化的环境的理解。

Development of competence for genetic transformation is the means by which bacteria are able to take up DNA from their environments. In this way, bacteria rapidly acquire novel genes or traits that may allow them to survive in harsh environments, make them resistant to antibiotics or become more virulent (able to cause diseases). The incorporation of exogenous DNA through transformation enable the bacteria to gain genetic variations, which is a major force to drive bacterial evolution. In addition, introduction of a genetically constructed DNA into a bacterial strain by genetic transformation is a widely used method in molecular cloning and other genetic manipulations in bacteria. Many bacteria are known to develop competence for genetic transformation. However, when bacteria develop competence to take up DNA and how this process is regulated are not fully understood. In the group of bacteria known as Streptococci, which tend to live on humans and animals, competence is known to be regulated by one of two signaling systems, the ComCDE and ComRS. Interestingly, Streptococcus mutans, a resident member in dental plaque, possesses both ComCDE and ComRS systems that are shown to regulate genetic competence. Recent work from our lab and from others further suggests that competence development in S. mutans and other related species is regulated at multiple levels, involving a complex regulatory network and multiple cross-connections among signalling transduction pathways. However, the molecular details of such a complex regulatory network is not fully elucidated. The proposed research aims to unravel this complex regulatory network in S. mutans. The results of this research will significantly advance our understanding of how bacteria to regulate their genetic plasticity, resist antibiotics and adapt to changing environments.