阪崎克罗诺肠杆菌血清学分型系统的扩展及关键致病因子的挖掘和分析

Cronobacter sakazakii can cause meningitis, sepsis and necrotizing enterocolitis in neonates, and the fatality rates due to C. sakazakii infection range between 40 to 80%. The recently established O-serotyping system of C. sakazakii only contains 7 serotypes and is hard to cover all isolated strains, which make it difficult to detect and monitor this important pathogen. Based on a large amount of previous work, this project will identify a series of new O-serotypes of C. sakazakii, as well as the new location sites of O-antigen encoding gene clusters in C. sakazakii genomes, which will extend the O-serotyping system of C. sakazakii. It is not only helpful for the detection and control of C. sakazakii in the field of infectious diseases prevention, but also useful in understanding the formation mechanism of C. sakazakii diversity. On this basis, we will systematically analyze the relationship between specific serotypes and virulence of C. sakazakii from two aspects. First, we will investigate whether and how the genes, which are specifically present in the genome of pathogenic C. sakazakii strains, contribute to the bacterial virulence. Second, we will analyze whether some special O-antigen structures can help strains to survive host attacks and adapt to environment. In summary, this project can give a more comprehensive insight into pathogenesis of C. sakazakii and provide a basis for prevention and treatment of C. sakazakii infections.

阪崎克罗诺肠杆菌可引起新生儿脑膜炎、败血病、坏死性小肠结肠炎等严重疾病，死亡率达40-80%，严重威胁新生儿健康。近期建立的阪崎克罗诺肠杆菌O血清学分型系统仅包括7个血清型，难以覆盖越来越多的分离菌株，给致病菌监测带来困难。本项目在大量前期工作基础上，鉴定阪崎克罗诺肠杆菌中一系列新的O血清型，并发现其基因组上新的O抗原基因簇位点，实现对该菌O血清学分型系统的扩展和完善，成果不但对致病菌防控意义重大，还有助于认识该致病菌的多样性形成机制。在此基础上，从两个角度系统分析阪崎克罗诺肠杆菌中部分血清型与菌株致病能力间的密切关系。一方面，分析多个前期发现的、在致病性菌株中特异存在的基因对于该菌致病能力的影响，并揭示其作用机制；另一方面，研究一些特殊的O抗原结构本身是否对于菌株逃避免疫攻击或适应宿主体内环境具有影响。上述研究将使我们更深入地了解该菌的致病机理，并为预防和治疗工作提供重要基础。

阪崎克罗诺肠杆菌可引起新生儿脑膜炎、败血病、坏死性小肠结肠炎等严重疾病，死亡率达40-80%，严重威胁新生儿健康。之前建立的阪崎克罗诺肠杆菌O血清学分型系统难以覆盖越来越多的分离菌株，给致病菌监测带来困难。本项目致力于对该菌O血清学分型系统的扩展和完善，并分析阪崎克罗诺肠杆菌中部分血清型与菌株致病能力间的密切关系。成果不但对致病菌防控有较重要意义，还有助于认识该致病菌的多样性形成机制。通过大规模的比较基因组学分析，我们发现了阪崎克罗诺肠杆菌中11个新血清型。解析了3个阪崎克罗诺肠杆菌新血清型的O抗原化学结构。在此基础上，建立了基于全基因组测序数据和液相芯片的阪崎克罗诺肠杆菌血清型分子检测技术，为该菌的检测、流行病学调查、溯源等提供了技术保障。此外，通过比较基因组学和实验分析，发现和鉴定了阪崎克罗诺肠杆菌中一系列与致病性相关的因子：发现强致病性阪崎克罗诺肠杆菌中特异性存在的一个致病因子ClkR，并揭示了该因子影响致病性的分子机理；发现阪崎克罗诺肠杆菌的RpoE通过调控鞭毛增强自身侵染能力和在巨噬细胞内的生存能力，从而影响致病性；发现阪崎克罗诺肠杆菌通过FepE和WzzB调控O抗原链长来影响细菌生物膜合成能力和干燥环境下的生存能力。.项目累计发表SCI论文12篇，项目负责人均为通讯作者。