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通过免疫蛋白质组分析鉴定产超广谱β-内酰胺酶肺炎克雷伯菌临床菌株的候选疫苗抗原

Identification of vaccine candidate antigens of an ESBL producing Klebsiella pneumoniae clinical strain by immunoproteome analysis.

作者信息

Kurupati Prathiba, Teh Boon King, Kumarasinghe Gamini, Poh Chit Laa

机构信息

Department of Microbiology, National University of Singapore, Singapore.

出版信息

Proteomics. 2006 Feb;6(3):836-44. doi: 10.1002/pmic.200500214.

DOI:10.1002/pmic.200500214
PMID:16372264
Abstract

Klebsiella pneumoniae is an opportunistic pathogen which causes pneumoniae, urinary tract infections and septicemia in immunocompromised patients. Hospital outbreaks of multidrug-resistant K. pneumoniae, especially those in neonatal wards, are often caused by strains producing the extended-spectrum-beta-lactamases (ESBLs). An immunoproteome based approach was developed to identify candidate antigens of K. pneumoniae for vaccine development. Sera from patients with acute K. pneumoniae infections (n = 55) and a control group of sera from healthy individuals (n = 15) were analyzed for reactivity by Western blot against ESBL K. pneumoniae outer membrane proteins separated by 2-DE. Twenty highly immunogenic protein spots were identified by immunoproteomic analysis. The immunogenic proteins that are most frequently recognized by positive K. pneumoniae sera were OmpA, OmpK36, FepA, OmpK17, OmpW, Colicin I receptor protein and three novel proteins. Two of the vaccine candidate genes, OmpA (Struve et al. Microbiology 2003, 149, 167-176) and FepA (Lai, Y. C. et al.. Infect Immun 2001, 69, 7140-7145), have recently been shown to be essential in colonization and infection in an in vivo mouse model. Hence, these two immunogenic proteins could serve as potential vaccine candidates.

摘要

肺炎克雷伯菌是一种机会致病菌,可在免疫功能低下的患者中引起肺炎、尿路感染和败血症。耐多药肺炎克雷伯菌在医院内的暴发,尤其是在新生儿病房的暴发,通常是由产生超广谱β-内酰胺酶(ESBLs)的菌株引起的。开发了一种基于免疫蛋白质组学的方法来鉴定肺炎克雷伯菌的候选抗原以用于疫苗开发。通过蛋白质印迹法分析了急性肺炎克雷伯菌感染患者(n = 55)的血清和健康个体对照组(n = 15)的血清与经二维电泳分离的产ESBL肺炎克雷伯菌外膜蛋白的反应性。通过免疫蛋白质组学分析鉴定出20个高免疫原性蛋白斑点。肺炎克雷伯菌阳性血清最常识别的免疫原性蛋白是外膜蛋白A(OmpA)、外膜孔蛋白K36(OmpK36)、铁摄取蛋白A(FepA)、外膜孔蛋白K17(OmpK17)、外膜蛋白W(OmpW)、大肠杆菌素I受体蛋白以及三种新蛋白。两个候选疫苗基因,即外膜蛋白A(Struve等人,《微生物学》2003年,第149卷,第167 - 176页)和铁摄取蛋白A(Lai,Y.C.等人,《感染与免疫》2001年,第69卷,第7140 - 7145页),最近已被证明在体内小鼠模型的定植和感染中至关重要。因此,这两种免疫原性蛋白可作为潜在的候选疫苗。

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