CexE is a 12 kDa protein that was originally reported to be present in just three strains of enterotoxigenic Escherichia coli (ETEC); a frequent cause of diarrheal illnesses worldwide. However, an examination of sequenced genomes has revealed that CexE is actually present in a majority of ETEC strains. In addition, homologs of CexE are present in enteroaggregative E. coli (EAEC), Yersinia enterocolitica, Providencia alcalifaciens, and Citrobacter rodentium. Although it has been hypothesized that CexE and its homologs are virulence factors, this has yet to be tested. Thus the primary aim of this study was to determine if these proteins contribute to pathogenicity. Our secondary aim was determine if they are secreted coat proteins. Here we report that all neonatal mice infected with a wild-type strain of C. rodentium perished. In contrast a cexE mutant was significantly attenuated with 45% neonate survival. In adult mice the wild-type strain reached significantly higher loads in the large intestines and were shed in greater numbers than cexE mutants. Secretion of the CexE homolog in EAEC is dependent upon an atypical Type I secretion system that accepts its client from the periplasm rather than the cytoplasm. Insertion mutants of cexC, the putative ATPase of the CexE secretion system, were attenuated in our murine model. In vitro we found that CexC is required for the secretion of CexE to the outer membranes of both ETEC and C. rodentium. Secretion is not constitutive because CexE accumulates in the periplasm when the two pathogens are cultured under noninducing conditions. Although secretion conditions differ between ETEC and C. rodentium, secreted CexE remains predominantly associated with the outer membranes of both species. In aggregate these findings demonstrate that CexE is a secreted coat protein and virulence factor that promotes colonization of host intestinal tissues by enteric pathogens.

CexE 是一种 12 kDa 蛋白质，最初报道仅存在于三种产肠毒素大肠杆菌 (ETEC) 菌株中；全世界腹泻疾病的常见原因。然而，对基因组测序的检查表明，CexE 实际上存在于大多数 ETEC 菌株中。此外，CexE 的同源物存在于肠聚集性大肠杆菌 (EAEC)、小肠结肠炎耶尔森氏菌、产碱普罗威登斯菌和啮齿类柠檬酸杆菌中。尽管有人假设 CexE 及其同源物是毒力因子，但这还有待测试。因此，本研究的主要目的是确定这些蛋白质是否有助于致病性。我们的次要目标是确定它们是否是分泌的外壳蛋白。在此，我们报告所有感染啮齿类野生型菌株的新生小鼠均死亡。相比之下，cexE 突变体显着减弱，新生儿存活率为 45%。在成年小鼠中，野生型菌株在大肠中的负荷明显更高，并且比 cexE 突变体排出的数量更多。 EAEC 中 CexE 同源物的分泌依赖于非典型的 I 型分泌系统，该系统从周质而不是细胞质接受其客户。 cexC（CexE 分泌系统的假定 ATP 酶）的插入突变体在我们的小鼠模型中被减弱。在体外，我们发现 CexC 是 ETEC 和啮齿类动物外膜 CexE 分泌所必需的。分泌不是组成型的，因为当两种病原体在非诱导条件下培养时，CexE 在周质中积累。尽管 ETEC 和 C. rodentium 之间的分泌条件不同，但分泌的 CexE 仍然主要与两个物种的外膜相关。 总的来说，这些发现表明 CexE 是一种分泌的外壳蛋白和毒力因子，可促进肠道病原体在宿主肠道组织中的定植。