Genetic, structural and functional analyses of flagellar glycosylation in epidemic Clostridium difficile strains

艰难梭菌是一种引起慢性腹泻和有时危及生命的疾病的细菌（通常称为C。艰难梭菌感染或CDI），主要发生在老年人和住院患者中。C.艰难梭菌现在是最普遍和最重要的医院获得性感染。考虑到C. CDI很难进化成高毒性，再加上人口老龄化和住院率的增加，CDI的问题可能会恶化。在过去十年中，CDI的报告发病率急剧上升，可能与侵袭性克隆菌株组的出现有关，例如所谓的PCR核糖体型027和017菌株。致病细菌通常有鞭毛。这种结构对运动性很重要，有助于向营养物质和远离有毒物质的方向游泳，但也对肠道病原体如C。艰难梭菌、鞭毛用于穿透肠细胞的粘液衬里。几种致病细菌的一个特征是它们的鞭毛被糖（聚糖）修饰，这赋予了多种特性，例如提高细菌的定殖能力，以及避免宿主免疫攻击。对具有攻击性的027和017菌株的遗传信息的仔细检查表明，它们进化出了不同的鞭毛聚糖，这可能部分解释了为什么它们如此成问题。我们将研究027和017菌株如何和为什么具有特异性鞭毛聚糖，以及鞭毛聚糖在生存和疾病能力中的潜在作用。梭很难对C.艰难梭菌的发现将加强我们对微生物和疾病的理解，并促进预防CDI的新治疗方法的开发。

Clostridium difficile is a bacterium that causes chronic diarrhoea and sometimes life-threatening disease (generally referred to as C. difficile infection or CDI) mainly in elderly and hospitalized patients. C. difficile is now the most prevalent and significant hospital acquired infection. Given the ability of C. difficile to evolve to be highly virulent coupled with the ageing population and increasing rates of hospitalization, the problem of CDI is likely to worsen. The reported incidence of CDI has risen dramatically over the last decade and is likely to be related to the emergence of aggressive sets of clonal strains such as the so-called PCR-ribotype 027 and 017 strains. Disease causing bacteria often have flagella. This structure is important for motility and facilitates swimming towards nutrients and away from noxious agents, but also for intestinal pathogens such as C. difficile, flagella are used to penetrate the mucus lining of intestinal cells. A feature of several disease causing bacteria is that their flagella are decorated with sugars (glycans), which confer multiple properties such as improved ability of the bacterium to colonise and also to avoid host immune attack. Scrutiny of the genetic information of the aggressive 027 and 017 strains suggests that they have evolved distinct flagellar glycans that may partly explain why they are so problematic.To help find ways to understand and prevent this disease, we will investigate how and why the 027 and 017 strains have specific flagellar glycans and the potential role of flagellar glycans in general in the survival and disease capability of C. difficile. A comprehensive understanding of flagellar glycosylation in C. difficile will strengthen our understanding of the microorganism and the disease as well as promoting the development of new treatments to prevent CDI.