Virulence factors of Clostridium difficile and their role during infection
Virulence factors of Clostridium difficile and their role during infection
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DOI：
10.1016/j.anaerobe.2015.10.009
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发表时间：
2016-02-01
期刊：
影响因子：
2.3
通讯作者：
Janoir, Claire
中科院分区：
文献类型：
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作者：
Janoir, Claire
艰难梭菌是医疗相关性腹泻的主要病原体。这种疾病的症状范围从轻度腹泻到危及生命的伪膜性结肠炎。耐药孢子污染后发生感染的主要风险因素是肠道微生物群的破坏，使孢子发芽。肠道的定殖可能受细菌对宿主反应的抗性和细菌对粘膜的粘附控制。迄今为止，已经鉴定出几种假定的粘附素，其中大多数显示MSCRAMM功能，并且粘附素突变体的研究清楚地强调了C.很难粘附到宿主上。鞭毛也参与了定殖过程，但它们的作用取决于测试的菌株。临床症状主要是由于两种大的葡萄糖基化毒素TcdA和TcdB，这是疾病表现所必需的。每种毒素的重要性根据菌株和实验条件而不同，但TcdB似乎是突出的一个，如突变体研究和不产生TcdA的致病菌株的自然发生所示。ADP核糖基化二元毒素的作用，表达的一些菌株，包括流行的谱系，是不清楚的，虽然它已与较高的发病率和死亡率。低水平的葡糖基化毒素和二元毒素的产生似乎促进对宿主细胞的粘附。tcdA和tcdB基因的表达受第二信使c-di-GMP的控制。其他毒力因子也是如此，特别是鞭毛、IV型皮利和一些粘附素基因。事实上，使用敲除突变体的几项研究表明，艰难梭菌在感染过程中可能经历粘附表型和运动表型之间的转换，由c-di-GMP细胞内水平调节。在体内，这可能导致生物膜形成，与孢子的持续存在相关，可能促进在至少20%的患者中观察到的复发的发生。(C)2015爱思唯尔有限公司版权所有。
Clostridium difficile is the prominent etiological agent of healthcare-associated diarrhea. The disease symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. The main risk factor for developing an infection after contamination by the resistant spores is the disruption of the gut microbiota, allowing the spores to germinate. The colonization of the gut is likely to be governed by the bacterial resistance to the host response and the bacterial adhesion to the mucosa. To date, several putative adhesins have been identified, most of them displaying MSCRAMM function, and studies of adhesin mutants have clearly underlined the multi-factorial feature of C. difficile adhesion to the host. Flagella have also been involved in the colonisation process, but their role depends on the tested strains. The clinical signs are mainly due to two large glucosylating toxins, TcdA and TcdB, which are essential for the disease manifestations. The importance of each toxin differs according to strains and experimental conditions, but TcdB seems to be the prominent one, as showed by mutant studies and the natural occurrence of pathogenic strains that do not produce TcdA. The role of the ADP ribosylating binary toxin expressed by some strains, including epidemic lineages, is not clearly established, although it has been related to higher morbidity and mortality. Production of low level of the glucosylating toxins and of the binary toxin seems to promote adhesion to host cells. Expression of the tcdA and tcdB genes is under the control of the second messenger c-di-GMP. This is also the case for other virulence factors, in particular for flagellar, pili type IV and some adhesin genes. Indeed, several studies using knock-out mutants suggest that C difficile may undergo a switch between the adhesion phenotype and the motility phenotype during the course of infection, regulated by the c-di-GMP intracellular level. In vivo, this could result in biofilm formation that, associated with persistence of spores, could promote the occurrence of relapses observed in at least 20% of patients. (C) 2015 Elsevier Ltd. All rights reserved.