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

艰难梭菌是一种主要在老年人和住院患者中引起慢性腹泻和有时危及生命的疾病(通常称为艰难梭菌感染或CDI)的细菌。艰难梭菌是目前最普遍和最重要的医院获得性感染。鉴于艰难梭菌能够进化为高毒力，加上人口老龄化和住院率上升，CDI问题可能会恶化。据报道，CDI的发病率在过去十年中急剧上升，可能与侵袭性克隆株的出现有关，如所谓的PCR型核糖体027和017株。致病细菌通常有鞭毛。这种结构对运动很重要，有助于游向营养物质和远离有害物质，但对于肠道病原体，如艰难梭菌，鞭毛被用来穿透肠道细胞的粘液衬里。几种致病细菌的一个特征是它们的鞭毛上装饰着糖(多糖)，这赋予了细菌多种属性，如提高细菌的定植能力，以及避免宿主免疫攻击。对具有攻击性的027和017菌株的遗传信息的研究表明，它们进化出了独特的鞭毛多糖，这可能部分解释了它们存在问题的原因。为了帮助找到理解和预防这种疾病的方法，我们将调查027和017菌株如何以及为什么具有特定的鞭毛多糖，以及鞭毛多糖在艰难梭菌的生存和疾病能力中的潜在作用。对艰难梭菌鞭毛糖基化的全面了解将加强我们对微生物和疾病的了解，并促进预防CDI的新疗法的开发。

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.