The role of flagella in Clostridium difficile pathogenesis: comparison between a non-epidemic and an epidemic strain.
The role of flagella in Clostridium difficile pathogenesis: comparison between a non-epidemic and an epidemic strain.
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DOI：
10.1371/journal.pone.0073026
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Minton NP
中科院分区：
文献类型：
--
作者：
Baban ST;Kuehne SA;Barketi-Klai A;Cartman ST;Kelly ML;Hardie KR;Kansau I;Collignon A;Minton NP
艰难梭菌是卫生保健相关感染的主要原因，并对全球卫生保健系统造成相当大的经济负担。疾病症状从自限性腹泻到致命性伪膜性结肠炎不等。而C.艰难梭菌具有两种主要的毒力因子，毒素A和B，但通常认为细菌的其它毒力组分也导致疾病。C.艰难梭菌在人和动物的肠道中定殖，因此粘附和定殖过程对于疾病发作是必不可少的。以前有人认为鞭毛可能与定殖有关。在这里，我们通过比较鞭毛亲本菌株与使用ClosTron技术灭活鞭毛基因的菌株来验证这一假设。我们的重点是在英国爆发，PCR核糖体型027（B1/NAP 1）菌株，R20291。我们比较了有鞭毛的野生型与具有瘫痪鞭毛的突变体以及在体外和体内不再产生鞭毛的突变体（fliC、fliD和flgE）。我们的研究结果与R20291提供了第一个强有力的证据，通过禁用电机的鞭毛，鞭毛的结构组成部分，而不是主动运动，需要在感染期间的肠上皮细胞的粘附和定殖。与已发表的630Δerm数据和我们自己的该菌株数据进行比较，发现菌株之间存在重大差异：R20291鞭毛突变体在体外的粘附力低于亲本菌株，而我们在630Δerm中看到了相反的情况。我们还表明，使用菌株630Δerm在体内成功定殖不需要鞭毛和运动性。最后，我们证明了在菌株R20291中，鞭毛确实在定殖和粘附中起作用，并且在C.艰难菌株后者强调了在得出关于特定发病机制的一般性结论之前，最重要的需要是表征不止一种菌株。
Clostridium difficile is a major cause of healthcare-associated infection and inflicts a considerable financial burden on healthcare systems worldwide. Disease symptoms range from self-limiting diarrhoea to fatal pseudomembranous colitis. Whilst C. difficile has two major virulence factors, toxin A and B, it is generally accepted that other virulence components of the bacterium contribute to disease. C. difficile colonises the gut of humans and animals and hence the processes of adherence and colonisation are essential for disease onset. Previously it has been suggested that flagella might be implicated in colonisation. Here we tested this hypothesis by comparing flagellated parental strains to strains in which flagella genes were inactivated using ClosTron technology. Our focus was on a UK-outbreak, PCR-ribotype 027 (B1/NAP1) strain, R20291. We compared the flagellated wild-type to a mutant with a paralyzed flagellum and also to mutants (fliC, fliD and flgE) that no longer produce flagella in vitro and in vivo. Our results with R20291 provide the first strong evidence that by disabling the motor of the flagellum, the structural components of the flagellum rather than active motility, is needed for adherence and colonisation of the intestinal epithelium during infection. Comparison to published data on 630Δerm and our own data on that strain revealed major differences between the strains: the R20291 flagellar mutants adhered less than the parental strain in vitro, whereas we saw the opposite in 630Δerm. We also showed that flagella and motility are not needed for successful colonisation in vivo using strain 630Δerm. Finally we demonstrated that in strain R20291, flagella do play a role in colonisation and adherence and that there are striking differences between C. difficile strains. The latter emphasises the overriding need to characterize more than just one strain before drawing general conclusions concerning specific mechanisms of pathogenesis.
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影响因子：
3.1
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通讯作者：
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