Amino acid substitutions in naturally occurring variants of ail result in altered invasion activity

Abstract

Yersinia enterocolitica is the causative agent of a variety of gastrointestinal syndromes ranging from acute enteritis to mesenteric lymphadenitis. In addition, systemic infections resulting in high mortality rates can occur in elderly and immunocompromised patients. More than 50 serotypes of Y. enterocolitica have been identified, but only a few of them commonly cause disease in otherwise healthy hosts. Those serotypes that cause disease have been divided into two groups, American and non-American, based on their geographical distributions, biotypes, and pathogenicity. We have been studying two genes, inv and ail, from Y. enterocolitica that confer in tissue culture assays an invasive phenotype that strongly correlates with virulence. Some differences between the American and non-American serotypes at the ail locus were noted previously and have been investigated further in this report. The ail locus was cloned from seven Y. enterocolitica strains (seven different serotypes). Although the different clones produced similar amounts of Ail, the product of the ail gene from non-American serotypes (AilNA) was less able to promote invasion by Escherichia coli than was the product of the ail gene from American serotypes (AilA). This difference is probably due to one or more of the eight amino acid changes found in the derived amino acid sequence for the mature form of AilNA compared with that of AilA. Seven of these changes are predicted to be in cell surface domains of the protein (a model for the proposed folding of Ail within the outer membrane is presented). These results are discussed in relation to the growing family of outer membrane proteins, which includes Lom from bacteriophage lambda, PagC from salmonella typhimurium, and OmpX from Enterobacter cloacae.

Application of Comparative Phylogenomics To Study the Evolution ofYersinia enterocoliticaand To Identify Genetic Differences Relating to Pathogenicity

“…In addition, the YE1818-to-YE1820 region was absent from all 35 biotype 1A strains (Fig. 3 contains a MacClade analysis of YE1820), confirming previous studies showing that the attachment-and-invasion locus (Ail) protein (YE1820) is absent from nonpathogenic isolates (5,45). The YE1818-to-YE1820 region encodes a transposase for the insertion sequence element IS1328, a hypothetical phage-related protein, and the well -characterized Ail protein (44).…”

“…No biotype 5 strains were tested, as they were absent from the study samples, and environmental biotype 1A isolates were not included in this study. A further eight human biotype 1B isolates of different serotypes originating from the United States were also included for analysis (5).…”

Epithelial Cell Adherence Mediated by the Enterotoxigenic Escherichia coli Tia Protein

“…One region of homology spans residues 78 to 96 of Tia in which 11 of 19 amino acids either are identical or represent conserved changes compared with Ail. The corresponding sequence of amino acids in Ail was predicted to reside in a loop that is exposed on the bacterial cell surface (2). In Tia, we predict that these 19 amino acids are also surface exposed (Fig.…”

Interaction of an Outer Membrane Protein of Enterotoxigenic Escherichia coli with Cell Surface Heparan Sulfate Proteoglycans

“…The group includes a number of virulence factors, including Ail (4,37) and the opacity-associated (Opa) proteins of Neisseria, to which Tia is most closely related (3). The Opa adhesins are a complex group of outer membrane proteins that are variably expressed in Neisseria.…”