Abstract:
:Conventional wisdom regarding mechanisms of bacterial pathogenesis holds that pathogens arise by external acquisition of distinct virulence factors, whereas determinants shared by pathogens and commensals are considered to be functionally equivalent and have been ignored as genes that could become adapted specifically for virulence. It is shown here, however, that genetic variation in an originally commensal trait, the FimH lectin of type 1 fimbriae, can change the tropism of Escherichia coli, shifting it toward a urovirulent phenotype. Random point mutations in fimH genes that increase binding of the adhesin to mono-mannose residues, structures abundant in the oligosaccharide moieties of urothelial glycoproteins, confer increased virulence in the mouse urinary tract. These mutant FimH variants, however, are characterized by increased sensitivity to soluble inhibitors bathing the oropharyngeal mucosa, the physiological portal of E. coli. This functional trade-off seems 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 environment, even at the cost of reduced physiological fitness in the nonpathologic habitat.
journal_name
Proc Natl Acad Sci U S Aauthors
Sokurenko EV,Chesnokova V,Dykhuizen DE,Ofek I,Wu XR,Krogfelt KA,Struve C,Schembri MA,Hasty DLdoi
10.1073/pnas.95.15.8922subject
Has Abstractpub_date
1998-07-21 00:00:00pages
8922-6issue
15eissn
0027-8424issn
1091-6490journal_volume
95pub_type
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