Bishop Anne L, Wiles Siouxsie, Dougan Gordon, Frankel Gad
Division of Cell and Molecular Biology, Flowers Building, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Microbes Infect. 2007 Sep;9(11):1316-24. doi: 10.1016/j.micinf.2007.06.006. Epub 2007 Jun 30.
Citrobacter rodentium belongs to a family of extracellular enteric pathogens that include enterohaemorrhagic and enteropathogenic Escherichia coli, which colonises the gastrointestinal mucosa by the attaching and effacing (A/E) mechanism. We previously described the appearance of a 'hyper-infectious' state after passage of C. rodentium through the murine gastrointestinal tract. Here we report that host-adapted C. rodentium is able to efficiently adhere and trigger actin polymerisation on cultured epithelial cells. Consistent with these observations we recorded higher levels of expression of genes carried on the LEE pathogenicity island and type III secretion system effector genes carried on prophages compared with in vitro-grown bacteria; importantly, the level of ler gene expression was unchanged. These phenotypes were lost after shed C. rodentium was adapted to the external environment. Upon exposure of C57Bl/6 mice, environmentally adapted C. rodentium was no longer infectious at the low doses associated with host-adapted bacteria and the bacteria were found to be localised in the caecal patch in a similar way to C. rodentium cultured in laboratory media. Thus, the 'hyper-infectious' host-adapted state, allowing efficient transmission and colonisation of naive hosts, is transient in nature and gradually lost after shedding into the environment.
鼠柠檬酸杆菌属于一类细胞外肠道病原体,其中包括肠出血性大肠杆菌和肠致病性大肠杆菌,它们通过紧密黏附并抹平(A/E)机制定殖于胃肠道黏膜。我们之前描述过鼠柠檬酸杆菌通过小鼠胃肠道传代后会出现“高感染性”状态。在此我们报告,适应宿主的鼠柠檬酸杆菌能够在培养的上皮细胞上高效黏附并触发肌动蛋白聚合。与这些观察结果一致,我们发现与体外培养的细菌相比,位于LEE致病岛的基因以及噬菌体携带的III型分泌系统效应基因的表达水平更高;重要的是,ler基因的表达水平没有变化。当排出的鼠柠檬酸杆菌适应外部环境后,这些表型就消失了。在用环境适应型鼠柠檬酸杆菌感染C57Bl/6小鼠后,其在与适应宿主的细菌相关的低剂量下不再具有感染性,并且发现这些细菌以与在实验室培养基中培养的鼠柠檬酸杆菌类似的方式定殖于盲肠淋巴集结。因此,这种允许对未感染宿主进行高效传播和定殖的“高感染性”适应宿主状态本质上是短暂的,在排入环境后会逐渐丧失。