van Diemen Pauline M, Dziva Francis, Stevens Mark P, Wallis Timothy S
Mammalian Enteric Pathogens Group, Division of Microbiology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, United Kingdom.
Infect Immun. 2005 Mar;73(3):1735-43. doi: 10.1128/IAI.73.3.1735-1743.2005.
Enterohemorrhagic Escherichia coli (EHEC) infections in humans are an important public health problem and are commonly acquired via contact with ruminant feces. The serogroups that are predominantly associated with human infection in the United States and Europe are O157 and O26. Serotypes O157:H7 and O26:H- differ in their virulence and tissue tropism in calves and therefore may colonize calves by distinct mechanisms. The mechanisms underlying EHEC intestinal colonization and pathogenesis are poorly understood. Signature-tagged mutagenesis was used to identify 59 genes of EHEC O26:H- that are required for the intestinal colonization of calves. Our results indicate important roles for locus of enterocyte effacement (LEE)-encoded type III secreted proteins in intestinal colonization. In addition, colonization is facilitated by cytotoxins, putative type III secreted proteins unlinked to the LEE, a putative fimbrial operon, and numerous genes involved in central metabolism and transport and genes of unknown function. Our data also imply that the elaboration of type I fimbriae by EHEC O26:H- is disadvantageous for persistence within the bovine intestines. These observations have important implications for the design of vaccines to control these important zoonotic pathogens.
人感染肠出血性大肠杆菌(EHEC)是一个重要的公共卫生问题,通常通过接触反刍动物粪便而感染。在美国和欧洲,主要与人类感染相关的血清型是O157和O26。血清型O157:H7和O26:H-在犊牛中的毒力和组织嗜性不同,因此可能通过不同机制在犊牛中定殖。EHEC肠道定殖和发病机制尚不清楚。利用签名标签诱变技术鉴定了EHEC O26:H-中59个在犊牛肠道定殖中必需的基因。我们的结果表明,肠细胞脱落位点(LEE)编码的III型分泌蛋白在肠道定殖中起重要作用。此外,细胞毒素、与LEE无关的假定III型分泌蛋白、假定的菌毛操纵子以及许多参与中心代谢和转运的基因和功能未知的基因也有助于定殖。我们的数据还表明,EHEC O26:H-产生I型菌毛不利于在牛肠道内持续存在。这些观察结果对控制这些重要人畜共患病原体的疫苗设计具有重要意义。