变异链球菌反义vicK调控白色念珠菌菌丝形成及共生生物膜致龋性的机制研究

变异链球菌和白色念珠菌是重要的龋病相关菌，VicRK系统是变异链球菌适应性及毒力表达调控的必需组成部分。申请人前期证实一条与变异链球菌vicK基因mRNA互补的反义RNA-ASvicK，并发现ASvicK过表达可干扰变异链球菌乳酸产生及白色念珠菌-变异链球菌共生生物膜菌丝形成、而外源性乳酸可促进白色念珠菌菌丝形成。那么，变异链球菌ASvicK是否可以通过调节乳酸产量调控白色念珠菌与变异链球菌交互作用及共生生物膜致龋性？是基于何种机制？为此，拟从以下方面进行功能和机制研究：1.变异链球菌ASvicK转录后调控vicK基因，进而干扰下游糖代谢通路及乳酸产生；2.ASvicK通过调节乳酸产量调控白色念珠菌与变异链球菌交互作用的效果及模式；3.ASvicK对共生生物膜体内致龋性的调控作用。本研究通过探索原核生物反义RNA调控模式，将为通过调节ASvicK变化从而控制牙菌斑生物膜致龋性提供理论依据。

Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) are caries-associated bacteria. And the VicRK 2-component system is crucial for bacterial adaptation and virulence; and the cognate sensor kinase VicK recognizes environmental stimuli in S. mutans. Notably, we identified an antisense vicK RNA (ASvicK). And we found that: ASvicK overexpression significantly impeded lactic acid production in S. mutans and hyphae growth in the cross-kingdom biofilm of C. albicans and S. mutans. In addition, lactic acid was proved an important substance to promote hyphae growth in C. albicans biofilm. Therefore, can S. mutans ASvicK regulate the interaction between C. albicans and S. mutans? and the cariogenicity of cross-kingdom biofilm? For that, we want to propose the functions and mechanisms studies from the following aspects: 1. ASvicK posttranscriptional regulates vicK gene, then interferes with downstream carbohydrate metabolism pathway and lactic acid production in S. mutans; 2. ASvicK regulates the interaction between C. albicans and S. mutans; 3. ASvicK regulates the cariogenicity of cross-kingdom biofilms in vivo. By exploring the regulatory mechanisms of antisense RNAs in prokaryotes, we can gain a new theoretical basis for controlling dental plaque by regulating ASvicK expression.