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艰难梭菌毒力与发病机制的新趋势

New trends in Clostridium difficile virulence and pathogenesis.

作者信息

Denève C, Janoir C, Poilane I, Fantinato C, Collignon A

机构信息

EA 4043, Université Paris-Sud, Châtenay-Malabry, France.

出版信息

Int J Antimicrob Agents. 2009 Mar;33 Suppl 1:S24-8. doi: 10.1016/S0924-8579(09)70012-3.

DOI:10.1016/S0924-8579(09)70012-3
PMID:19303565
Abstract

The disease spectrum caused by Clostridium difficile infection ranges from antibiotic-associated diarrhoea to life-threatening clinical manifestations such as pseudomembranous colitis. C. difficile infection is precipitated by antimicrobial therapy that causes a disruption of the normal colonic microbiota, predisposing to C. difficile intestinal colonisation. The pathogenicity of C. difficile is mediated by two exotoxins, TcdA and TcdB, both of which damage the human colonic mucosa and are potent cytotoxic enzymes. C. difficile must first be implanted in the gut and attach to epithelial cells, which are protected by a layer of dense mucus. Confirmed and putative accessory virulence factors that could play a role in adherence and intestinal colonisation have been identified and include proteolytic enzymes and adhesins. Recently, the epidemiology of C. difficile infection has radically changed and an increased incidence is associated with outbreaks in North America and Europe. Several reports suggest that disease severity is increasing to include sepsis syndrome and toxin megacolon. Elderly, debilitated patients in hospitals and nursing homes are particularly vulnerable. A hypervirulent, epidemic strain has been associated with the changing epidemiology and severity of disease. Here, we review the characteristics of the epidemic NAP1, PCR ribotype 027 C. difficile strain that could explain its hypervirulence and epidemic spread.

摘要

艰难梭菌感染所引发的疾病谱范围广泛,从抗生素相关性腹泻到诸如伪膜性结肠炎等危及生命的临床表现。艰难梭菌感染是由抗菌治疗引发的,抗菌治疗会破坏正常的结肠微生物群,从而易引发艰难梭菌在肠道的定植。艰难梭菌的致病性由两种外毒素TcdA和TcdB介导,这两种外毒素都会损害人类结肠黏膜,并且是强效细胞毒性酶。艰难梭菌必须首先在肠道中定植并附着于上皮细胞,而上皮细胞受到一层致密黏液的保护。已鉴定出可能在黏附和肠道定植中发挥作用的已确认和假定的辅助毒力因子,包括蛋白水解酶和黏附素。最近,艰难梭菌感染的流行病学发生了根本性变化,北美和欧洲的发病率上升与疫情爆发有关。几份报告表明,疾病严重程度正在增加,包括脓毒症综合征和毒素性巨结肠。医院和养老院中的老年体弱患者尤其易受影响。一种高毒力流行菌株与疾病流行病学和严重程度的变化有关。在此,我们综述了流行的NAP1、PCR核糖型027艰难梭菌菌株的特征,这些特征可以解释其高毒力和流行传播情况。

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