Molecular evolution and mosaic structure of alpha, beta, and gamma intimins of pathogenic Escherichia coli

Two types of pathogenic Escherichia coli, enteropathogenic E. coli (EPEC) a nd enterohemorrhagic E. coli (EHEC), cause diarrheal disease by disrupting the intestinal environment through the intimate attachment of the bacteria to the intestinal epithelium. This process is mediated by intimin, an outer membrane protein that is homologous to the invasins of pathogenic Yersinia . The intimin (eae) gene is part of a pathogenicity island, a 35-kb segment of DNA that has been acquired independently in different groups of pathoge ns. Nucleotide sequences of eae of three EPEC and four EHEC strains represe nting distinct clonal lineages revealed an exceptionally high level of dive rgence (15%) in the amino acid sequences of alpha, beta, and gamma intimin molecules, most of which is concentrated in the C-terminal region. The gamm a intimin sequences from E. coli strains with serotypes O157:H7, O55:H7, an d O157:H- are virtually identical, supporting the hypothesis that these bac teria belong to a single clonal lineage. Sequences of beta intimin of EPEC strains of serotypes O111:H2 and O128:H2 show substantial differences from alpha and gamma intimins, indicating that these strains have evolved indepe ndently. Strong nonrandom clustering of polymorphic sites indicates that th e intimin genes are mosaics, suggesting that protein divergence has been ac celerated by recombination and diversifying selection.