葡萄糖影响SaeRS介导的表皮葡萄球菌自溶机制研究

Staphylococcus epidermidis is a major cause of nosocomial infections because of biofilm formation. In our previous research, for the first time we found that two-component signal transduction system SaeRS regulated S. epidermidis biofilm formation, autolysis and glucose metabolism. S. epidermidis saeRS gene deletion mutant which was constructed by homologous recombination, showed obvious lower viability, significantly higher Triton X-100 induced autolysis ability and increased susceptibility to penicillin. SaeRS positively regulate glucose metabolism. We postulate that saeRS influence autolysis and biofilm formation by regulating glucose metabolism. The current project proposal plans to analyze further that (1) whether glucose metabolism can influence the autolysis and survival ability of saeRS mutant; (2) whether SaeRS regulate autolysis through ccpA –lrg/cid pathway which plays a centrol role in glucose metabolism; (3) the S. epidermidis saeRS mutant autolysis in animal model in response to glucose. Our findings would shed new lights on the mechanism of S. epidermidis autolysis formation, and provide basis for the therapy of S. epidermidis infection.

表皮葡萄球菌院内感染及耐药与生物膜形成密切相关。前期研究发现双组分信号转导系统SaeRS可调控表皮葡萄球菌生物膜形成能力、自溶和葡萄糖的代谢。表皮葡萄球菌saeRS基因删除突变株生存能力与野生株相比明显降低，自溶率增加，并对青霉素类抗生素敏感性增加。SaeRS正向调控细菌葡萄糖代谢过程，提示葡萄糖在SaeRS介导的表皮葡萄球菌自溶及生物膜形成中起重要作用。本研究拟分析：①葡萄糖代谢是否能影响saeRS突变株的自溶及生存能力；②分析表皮葡萄球菌SaeRS是否通过ccpA-lrg/cid通路调控葡萄糖代谢，从而进一步影响细菌自溶；③新西兰白兔生物膜感染模型验证葡萄糖作用下SaeRS在表皮葡萄球菌自溶形成中起的作用。该研究将有助于阐明葡萄糖影响表皮葡萄球菌自溶形成的机制，并为表皮葡萄球菌感染的治疗提供思路。

表皮葡萄球菌是随着人口老龄化而出现的医院内感染重要的致病菌，表皮葡萄球菌生物膜的形成和耐药株的产生机制已成为亟需解决的重大科学问题。表皮葡萄球菌在抗生素治疗时可变为休眠状态，即形成所谓的持留菌。本项目主要研究SaeRS影响表皮葡萄球菌生存、生物膜、及持留菌形成的机制，主要探讨在生物膜中saeRS对持留菌形成信号转导通路的影响。本研究构建了表皮葡萄球菌saeRS基因删除突变株，通过基因芯片技术分析了saeRS调控的基因表达谱，并分析了saeRS基因对表皮葡萄球菌感受态转化能力及抗生素敏感能力的影响，另外已成功构建新西兰白兔生物膜感染模型，并初步分析了saeRS突变株在新西兰白兔体内抵抗抗生素的能力。目前正在验证saeRS-ccpA-cid/lrg通路对表皮葡萄球菌生物膜和持留菌形成的影响及机制。本项目聚焦于葡萄球菌持续性感染形成和维持的关键环节，深入研究和揭示葡萄球菌形成和维持持续性感染过程中生物膜的形成及调控、双组分信号转导系统SaeRS调控细菌的感受状态进而影响细菌的自溶及对抗生素的敏感性等关键环节的分子机制，为防治相关微生物感染与传播提供了科学依据和技术支撑。

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