Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin.
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.
Sokurenko
E V
EV
Department of Anatomy and Neurobiology, University of Tennessee, Memphis, TN 38163, USA.
Chesnokova
V
V
Dykhuizen
D E
DE
Ofek
I
I
Wu
X R
XR
Krogfelt
K A
KA
Struve
C
C
Schembri
M A
MA
Hasty
D L
DL
D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism; D018830:Adhesins, Escherichia coli; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity*; D005260:Female; D036781:Fimbriae Proteins; D006168:Guinea Pigs; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D001743:Urinary Bladder / Q000382:microbiology
D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D011956:Receptors, Cell Surface; C058769:fimH protein, E coli; D036781:Fimbriae Proteins