PATHOGENIC ADAPTATION OF ESCHERICHIA-COLI BY NATURAL VARIATION OF THEFIMH ADHESIN

Conventional wisdom regarding mechanisms of bacterial pathogenesis hol ds that pathogens arise by external acquisition of distinct,virulence factors, whereas determinants shared by pathogens and commensals are c onsidered to be functionally equivalent and have been ignored as genes that could become adapted specifically for virulence. It is shown her e, however, that genetic variation in an originally commensal trait, t he FimH lectin of type 1 fimbriae, can change the tropism of Escherich ia coli, shifting it toward a urovirulent phenotype, Random point muta tions in fimH genes that increase binding of the adhesin to mono-manno se residues, structures abundant in the oligosaccharide moieties of ur othelial glycoproteins, confer increased virulence in the mouse urinar y tract. These mutant FimH variants, however, are characterized by inc reased sensitivity to soluble inhibitors bathing the oropharyngeal muc osa, the physiological portal of E. coli. This functional trade-off se ems to be detrimental for the intestinal ecology of the urovirulent E. coli, Thus, bacterial virulence can be increased by random functional mutations in a commensal trait that are adaptive for a pathologic env ironment, even at the cost of reduced physiological fitness in the non pathologic habitat.