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. 1 , Chesnokova V. 1, 8 , Dykhuizen D.E.3 , Ofek I.4 , Wu X.-R.5 , Krogfelt K.A.6 , Struve G.6 , Schembri M.A.7 , Hasty D.L.1, 2, 9
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  • 1 Dept. of Anatomy and Neurobiology, University of Tennessee, Memphis, TN 38163, United States
  • 2 Research Service (151), Dept. of Vet.' Aff. Medical Center, Memphis, TN 38104, United States
  • 3 Department of Ecology and Evolution, State University of New York, Stony Brook, NY 11794, United States
  • 4 Department of Human Microbiology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
  • 5 Department of Urology, New York University, School of Medicine, New York, NY 10016, United States
  • 6 Department of Medical Bacteriology, Statens Serum Institute, 5 Artillerivej, 2300 Copenhagen S, Denmark
  • 7 Department of Microbiology, Technical University of Denmark, Lyngby, DK-2800, Denmark
  • 8 Department of Microbiology, Nations Friendship University, Moscow, Russian Federation
  • 9 Research Service (151), Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, United States
Ключевые слова
bacterial protein; animal cell; bacterial virulence; conference paper; controlled study; escherichia coli; gene expression; genetic variability; nonhuman; pathogenesis; point mutation; priority journal; protein expression; Adhesins, Bacterial; Adhesins, Escherichia coli; Alleles; Amino Acid Sequence; Animals; Bacterial Adhesion; Escherichia coli; Female; Fimbriae Proteins; Guinea Pigs; Mice; Mice, Inbred C3H; Molecular Sequence Data; Mutation; Phenotype; Receptors, Cell Surface; Urinary Bladder; Animalia; Bacteria (microorganisms); Escherichia coli; Negibacteria
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