Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin - PubMed (original) (raw)

Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin

E V Sokurenko et al. Proc Natl Acad Sci U S A. 1998.

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.

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Figures

Figure 1

Figure 1

Colonization of mouse bladders by isogenic E. coli expressing nonfunctional FimH, M1L FimH, or M1H FimH subunits. Bars indicate mean cfu per bladder ± SEM. P values indicating level of significance between different groups are indicated.

Figure 2

Figure 2

Inhibition of interaction of E. coli and buccal cells by α-methyl-

d

-mannopyranoside.

Figure 3

Figure 3

Inhibition of the interaction of E. coli and buccal cells by whole, stimulated human saliva.

Figure 4

Figure 4

Phylogenetic analysis of FimH alleles. (A) Amino acid sequences of FimH variants. The alleles are listed based on an increasing M1:M3 binding ratio. The residues listed above the 11 alleles are for the amino acids in original FimH sequence (17) that vary in the other fimH alleles. Only polymorphic residues are shown, and the positions are numbered vertically, from −16 to +201. ▵, deleted residues. (B) Inferred phylogenetic network demonstrating evolutionary relationships of the FimH alleles shown in A. Each node represents a distinct FimH allele, numbered as in A. The allele labeled n represents a hypothetical FimH that differs from allele #2 by the substitution of Asp (N) for Tyr (T) in the leader sequence (residue, −16) and phenotypically should be equivalent to allele #2. Internal nodes are shown in bold. The deduced sequences of the 11 FimH proteins exhibit greater than 99% homology, and the network showing their phylogenetic relationships is fully consistent, without any homoplasty. Branch lengths are scaled to the number of amino acids that differ between alleles, as indicated. The deletion of 4 amino acids in FimH allele #10 is considered to be a single event, equivalent to one amino acid substitution.

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