Abstract
Class 5 fimbriae of enterotoxigenic Escherichia coli (ETEC) comprise eight serologically discrete colonization factors that mediate small intestinal adhesion. Their differentiation has been attributed to the pressure imposed by host adaptive immunity. We sequenced the major pilin and minor adhesin subunit genes of a geographically diverse population of ETEC elaborating CFA/I (n = 31), CS17 (n = 20), and CS2 (n = 18) and elucidated the functional effect of microevolutionary processes. Between the fimbrial types, the pairwise nucleotide diversity for the pilin or adhesin genes ranged from 35-43%. Within each fimbrial type, there were 17 non-synonymous and 1 synonymous point mutations among all pilin or adhesin gene copies, implying that each fimbrial type was acquired by ETEC strains very recently, consistent with a recent origin of this E. coli pathotype. The 17 non-synonymous allelic differences occurred in the CFA/I pilin gene cfaB (two changes) and adhesin gene cfaE (three changes), and CS17 adhesin gene csbD (12 changes). All but one amino acid change in the adhesins clustered around the predicted ligand-binding pocket. Functionally, these changes conferred an increase in cell adhesion in a flow chamber assay. In contrast, the two mutations in the non-adhesive CfaB subunit localized to the intersubunit interface and significantly reduced fimbrial adhesion in this assay. In conclusion, naturally occurring mutations in the ETEC adhesive and non-adhesive subunits altered function, were acquired under positive selection, and are predicted to impact bacteria-host interactions.
Highlights
Class 5 fimbriae of enterotoxigenic Escherichia coli (ETEC) represent important colonization factors that mediate small intestinal adhesion
Some clades were composed of distinct ETEC sequence type (ST), whereas others contained a mixture of ETEC, other diarrheagenic E. coli pathotypes and non-pathogenic isolates (Fig. 1)
We show that the diversity of pilin and adhesin genes between three class 5 fimbrial types was high, whereas there was very low diversity within any particular fimbrial type, and this diversity was associated with functional adaptation
Summary
Class 5 fimbriae of ETEC represent important colonization factors that mediate small intestinal adhesion. Class 5 fimbriae of enterotoxigenic Escherichia coli (ETEC) comprise eight serologically discrete colonization factors that mediate small intestinal adhesion. Their differentiation has been attributed to the pressure imposed by host adaptive immunity. One approach to elucidating structure-function relationships of bacterial adhesins as it relates to pathogenesis is to examine the functional impact of naturally occurring mutations that are acquired under positive selection (20 –22). Such pathoadaptive mutations represent an alternative mechanism of virulence evolution, complementing horizontal gene transfer. Our findings underscore common themes in microevolution of fimbrial adhesins from different pathotypes of E. coli
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