中国医院获得性(HA)-MRSA在医院内定植进而引发持续感染的分子机制是目前研究热点。申请人前期研究发现SpA蛋白在临床HA-MRSA流行株ST239中显著高表达，SpA促进ST239在宿主鼻腔内定植及宿主细胞内滞留和抗杀伤, 提示SpA在ST239持续性定植感染中扮演重要角色。要明确SpA促进HA-MRSA持续定植感染的具体分子机制，课题组将在构建一系列基因突变株及互补表达株、以及获得纯化蛋白及多克隆抗体基础上，从体外和体内实验角度阐明中国HA-MRSA流行株ST239高表达SpA的具体调控机制，宿主细胞内SpA通过调动哪些宿主效应分子促进细菌在宿主细胞内滞留和抗杀伤以及SpA与效应分子相互作用可能的伴侣蛋白/衔接蛋白。研究成果为补充和完善金葡菌致病因子的调控网络、为HA-MRSA如何引起持续性感染的机制提供新的实验依据。最终为及时诊断与感控措施实施及设计新的抗感染药物或疫苗提供药靶。

Emergence of hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) epidemic clone ST239 infection in healthcare facilities has been noted recently. Persistent colonization is an important risk factor for HA-MRSA infection. Our previous studies suggested that clinical HA-MRSA ST239 has a high level production of Staphylococcus protein A (SpA), the preliminary experiment verified that SpA played a significant role in nasal colonization, intracellular retention and resistance to phagocytosis of ST239, indicating that SpA is an essential factor for persistent colonization of ST239. However, the genes regulatory mechanism of high expression of SpA in HA-MRSA ST239 and SpA mobilize which effector molecules promoting intracellular bacterial retention and anti-killing, as well as the possible chaperone / adaptor proteins which interaction with SpA remained to be clarified. Our research group aims to elucidate the molecular mechanism of SpA promoting hospital acquired HA-MRSA epidemic clone ST239 persistent colonization based on the acquisition of spa gene mutant, complementary strain, purified proteins and polyclonal antibodies. In vivo experiment further confirm the impact of SpA on colonization, virulence of HA-MRSA ST239. All these results will provide new experimental evidences for supplementing the regulatory network of S. aureus virulence factors and the mechanism of persistent infections of S.aureus.