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摄取DNA的手段。通过这种方式，细菌迅速获得新的基因或特征，使它们能够在恶劣的环境中生存，使它们对抗生素产生抗性或变得更具毒性（能够引起疾病）。外源DNA通过转化的方式进入细菌体内，使细菌获得遗传变异，这是细菌进化的主要动力。此外，通过遗传转化将遗传构建的DNA引入细菌菌株中是细菌中的分子克隆和其它遗传操作中广泛使用的方法。已知许多细菌具有遗传转化的能力。然而，细菌何时发展出摄取DNA的能力以及这一过程是如何被调节的还没有完全了解。在一组被称为链球菌的细菌中，它们倾向于生活在人类和动物身上，已知能力受到两种信号系统之一的调节，ComCDE和ComRS。有趣的是，变形链球菌，在牙菌斑中的居民成员，具有两个ComCDE和ComRS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研究进一步表明，S。变形杆菌和其他相关物种在多个水平上受到调控，涉及复杂的调控网络和信号转导途径之间的多重交叉连接。然而，这样一个复杂的调控网络的分子细节并没有完全阐明。这项研究的目的是解开S.变异人这项研究的结果将大大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.