Molecular basis of commensalism in the urinary tract: low virulence or virulence attenuation? - PubMed (original) (raw)

Molecular basis of commensalism in the urinary tract: low virulence or virulence attenuation?

Jaroslaw Zdziarski et al. Infect Immun. 2008 Feb.

Abstract

In some patients, Escherichia coli strains establish significant bacteriuria without causing symptoms of urinary tract infection (UTI). These asymptomatic-bacteriuria (ABU) strains have been shown to express fewer virulence factors than the uropathogenic E. coli (UPEC) strains that cause severe, symptomatic UTI. Paradoxically, ABU strains carry many typical UPEC virulence genes, and the molecular basis of their low virulence therefore remains unclear. This study examined whether ABU strains might evolve from UPEC by genome loss and virulence gene attenuation. The presence of conserved E. coli K-12 genes was examined using an E. coli K-12 strain MG1655-specific DNA array and the distribution of UPEC virulence-related genes was examined with the E. coli pathoarray. Two groups of strains could be distinguished. Several ABU strains were shown by multilocus sequence typing and by comparative genomic analyses to be related to UPEC but to have smaller genome sizes. There were significant alterations in essential virulence genes, including reductive evolution by point mutations, DNA rearrangements, and deletions. Other strains were unrelated to UPEC and lacked most of the virulence-associated genes. The results suggest that some ABU strains arise from virulent strains by attenuation of virulence genes while others are nonvirulent and resemble commensal strains. We propose that virulence attenuation might constitute a general mechanism for mucosal pathogens to evolve toward commensalism.

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Figures

FIG. 1.

FIG. 1.

Genomic alterations among ABU E. coli isolates. White and black denote the presence and absence, respectively, of genes detected by CGH. The dendrogram shows the estimated genomic relationships of the different strains obtained by hierarchical cluster analysis.

FIG. 2.

FIG. 2.

Genomic fingerprints of ABU E. coli isolates. The similarity of the genome structure was assessed by BOX-PCR (A) and PFGE (B) following XbaI digestion. To analyze the genome structure similarity among closely related ST 73 isolates, UPEC strain CFT073 and nonpathogenic strain Nissle 1917 were used as references.

FIG. 3.

FIG. 3.

Genetic structures of the fim determinant and the adjacent KpLE2 phage region in ABU E. coli isolates. The scheme is based on the E. coli K-12 chromosome. The filled (gray to white) arrows denote genes of the fim determinant, filled gray arrows denote ORFs of the KpLE2 prophage, filled white to black arrows denote the fec determinant located within KpLE2, and black arrows denote ORF A and nonfunctional ORF B of the ISEhe3-like element, which replaces large regions of KpLE2 in ABU strains 21 and 38.

FIG. 4.

FIG. 4.

Genotypic and phenotypic diversity among closely related members of the E. coli clonal group (ST 73). The high E. coli genome plasticity results in marked phenotypic variability among individual members of the same ST, which thus includes pathogenic and nonpathogenic variants. Genome reduction/loss of function contributes to the evolution of these ABU variants from uropathogenic ancestors. fim, type 1 fimbrial determinant; pap, P fimbrial determinant; papG, P fimbrial adhesin-encoding gene; foc, F1C fimbrial determinant; focD, F1C fimbrial usher-encoding gene.

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