VanRS双组分系统在VanA型万古霉素耐药性肠球菌中的调控机制研究

糖肽类抗生素万古霉素通常作为治疗G+菌感染的最后一道防线，而近年来万古霉素耐药性肠球菌的感染日趋严重，成为临床治疗的难点。万古霉素耐药性源于VanRS双组分严谨型调控系统对胞外的抗生素做出应答而激活vanAHX结构基因簇的表达。在前期研究中我们发现，VanA型VRE菌株V309中的VanRS双组分系统可被万古霉素诱导，发生自我磷酸化并激活vanAHX的表达；而出乎意料的是，在无万古霉素诱导时vanA基因簇同样具有高水平的表达活性，这表明V309中的VanRS双组分系统可能在活性上发生了改变，或者存在VanRS双组分系统的交叉调节。本研究拟在前期研究基础上，深入分析VRE的耐药调控机制。通过对VanR、VanS的表达情况、功能及相互作用的研究，阐明VanRS双组分系统的功能及应答机制，为进一步从分子水平阻断VanA酶的产生，有效解决VRE耐药问题提供理论依据。

Vancomycin is considered to be the last line of defense for therapying infections due to gram positive bacteria. Infections caused by Vancomycin-Resistant Enterococci are reported in an increasing number and the therapeutic measure is limited. Vancomycin resistance attributed to expression of the resistance genes of the vanAHX clusters is regulated by the VanRS two-component regulatory systems.The VanRS two-component signal transduction system in VanA-Type Vancomycin-Resistant Enterococci V309 were studied in early stage. To our surprise, the vanAHX clusters in V309 can be expressed without inducement of vancomycin. This phenomenon indicated that the activation of VanRS two-component regulatory systems of V309 maybe changed to some extent, or the VanRS systems could "cross-talk" with other two-component regulatory systems in cell. So we want to further analyse the VanRS system and the resistance regulatory mechanism of VRE, to clarify the expression of VanR and VanS protein and it's function. Our study can provide theoretical basis for restraining production of VanA enzyme and resolving vancomycin-resistant problem.