变异链球菌生物膜离散分子的研究

Biofilm can enable the survival and the sustained pathogenic ability of pathogens. It is also closely related to chronic and recalcitrant infections, medical implant-related infections and antibiotic resistance. Since Streptococcus mutans (S. mutans) has been reported as an opportunistic pathogen associated with human dental caries, how to control the biofilm of S. mutans has become one of the key research directions of dental caries. A novel biofilm control strategy is to utilize compounds for inducing the shift from biofilm to a planktonic mode of life followed by using an antimicrobial agent to kill the dispersed organisms. How to initiate S. mutans biofilm dispersal? Inspired by biofilm dispersal, a part of the natural biofilm development cycle, we hypothesize that if it’s possible to find self-produced biofilm dispersal molecules that can trigger S. mutans biofilm dispersal. According to the hypothesis above, we plan to conduct the bacterial transcriptome analysis of different stages of biofilm development and use the results as reference for subsequent metabolomics analysis. Then the supernatants of biofilm dispersal will be analyzed by metabolomics followed by biofilm dispersal molecules screening and identifying. The biofilm dispersal molecules of S. mutans will be also used to explore their effects on biofilm dispersal of other common pathogens. This is the first research of self-produced molecules that trigger S. mutans biofilm dispersal and it is also the first study to explore the effect of biofilm dispersal molecules of S. mutans on the disassembly of other common pathogens biofilm. The indentified biofilm dispersal molecules of S. mutans will have good application prospects for controlling dental caries. What’s more, it will also provide reference to design drugs to control caries and study of other common pathogens-related biofilm dispersal molecules.

生物膜是致病菌应对外界复杂环境并持续发挥其毒力的基本保障，与慢性细菌性感染、医用植入材料相关感染及抗生素耐药现象都密切相关。变异链球菌是公认的条件致龋菌，如何防治变异链球菌的生物膜也成了龋病研究的重点方向之一。生物膜离散结合抗菌药物杀死离散的细菌是生物膜防治的新策略，如何使变异链球菌生物膜发生离散呢？我们将目光投向了变异链球菌生物膜生命周期中的离散过程，可否从该过程中找到变异链球菌自身产生的离散分子呢？针对上述问题，我们计划以生物膜不同周期细菌转录组分析为参考；对生物膜离散时的上清液进行代谢组学分析、筛选出离散分子，对其功能进行验证并探索其对其他常见致病菌生物膜离散作用。本课题首次研究变异链球菌自身产生的生物膜离散分子并探索其离散作用的广谱性；成功鉴定的变异链球菌生物膜离散分子将具有良好的龋病防治应用前景；也可为龋病防治药物的设计和其他病原菌生物膜离散分子的研究提供参考。

生物膜是致病菌应对外界复杂环境并持续发挥其毒力的基本保障，与慢性细菌性感染、医用植入材料相关感染及抗生素耐药现象都密切相关。变异链球菌是公认的条件致龋菌，如何防治变异链球菌生物膜及调控菌斑微生态也成了龋病研究的重点方向之一。本项目研究了生物膜离散分子去假亚精胺、无花果蛋白酶、顺式-2-葵烯酸和新型抗菌药物SCH-79797等对变异链球菌及相关生物膜的形成、离散的作用，检测了变异链球菌生物膜的离散周期。结果表明仅顺式-2-葵烯酸对变异链球菌生物膜具有离散作用，但这些生物膜离散分子可显著抑制变异链球菌生物膜的形成、致龋毒力和基因表达；去甲亚精胺、SCH-79797不仅可以抑制变异链球菌生物膜的形成，而且可调控变异链球菌和血链球菌双菌种生物膜的组成和致龋毒力，具有一定的菌斑生态调控功能。此外，变异链球菌生物膜在8-10天出现离散现象。这些研究结果将有助于评估这些生物膜离散分子用于龋病防治的潜能。