Microevolution in fimH gene of mucosa-associated Escherichia coli strains isolated from pediatric patients with inflammatory bowel disease - PubMed (original) (raw)

Microevolution in fimH gene of mucosa-associated Escherichia coli strains isolated from pediatric patients with inflammatory bowel disease

Valerio Iebba et al. Infect Immun. 2012 Apr.

Abstract

Several studies reported increased numbers of mucosa-associated Escherichia coli strains in patients with inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC). The majority of E. coli strains possess type 1 fimbriae, whose tip fibrillum protein, FimH, naturally undergoes amino acid replacements, an important process in the adaptation of commensal E. coli strains to environmental changes, like those observed in IBD and urinary tract infections. In this study, we analyzed mutational patterns in the fimH gene of 52 mucosa-associated E. coli strains isolated from IBD and non-IBD pediatric patients, in order to investigate microevolution of this genetic trait. FimH-positive strains were also phylogenetically typed and tested for their adhesive ability on Caco-2 cells. Specific FimH alleles for each grouping feature were found. Mutations G66S and V27A were related to CD, while mutations A242V, V163A, and T74I were attributed to UC. Otherwise, the G66S, N70S, and S78N mutations were specifically attributed to B2/D phylogroups. The N70S and A119V mutations were related to adhesive E. coli strains. Phylogroup B2, adhesive, and IBD E. coli strains showed a higher site substitution rate (SSR) in the fimH gene, together with a higher number of mutations. The degree of naïve mucosal inflammation was related to specific FimH alleles. Moreover, we could suggest that the V27A mutation is pathoadaptive for the CD intestinal habitat, while we could also suggest that both the N70S and S78N mutations are related to the more virulent E. coli B2 phylogroup. In conclusion, we found some FimH variants that seem to be more involved than others in the evolution of IBD pathogenesis.

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Figures

Fig 1

Fig 1

Discriminating amino acid mutations in FimH protein. A three-dimensional graphical representation of the low-affinity state of FimH protein (Protein Data Bank accession number 3JWN) showed amino acid residues with the power to discriminate a patient's status (A) (red, CD; blue, UC), the E. coli phylogroup (B) (red, B2/D; blue, A/B1), and the E. coli for adhesion capability (C) (red, class 2). The donor strand of the FimG protein, which incorporates into the pilin β-barrel domain, is depicted in green.

Fig 2

Fig 2

Clustered image mapping of fimH gene mutation weights. Simca-P+ software was used to compute weight coefficients for each mutation (70 x variables) on a patient's status (3 y variables) with a scaled and centered data set. These coefficients were useful to interpret the influence of the x variables on the y ones. Coefficients for different responses (y variables) were also comparable, as the y variables were normalized (scaled). As depicted in the color-coded legend, the higher that the coefficient value is, the higher the weight (red), while the lower that the value is, the lower the weight (turquoise).

Fig 3

Fig 3

Bayesian phylogenetic tree. A Bayesian tree generated by Geneious (version 4.8.3) software as described in Materials and Methods is depicted. This rooted phylogenetic tree of the fimH sequences of 52 strains (plus the fimH sequences of strains MG1655 and LF82) showed four distinct groups: NT1a, NT1b (NT1a and NT1b were joined into NT1 in the text for SSR analysis), NT2, and NT3. These groups were progressively denoted from higher SSRs to lower ones. Inside each group, depicted with an ellipse, were reported the amino acid mutations found in ≥90% of strains belonging to the group itself. The black circle indicates the root.

Fig 4

Fig 4

Correlation of fimH gene mutability and PCDAI. PCDAI was correlated to the mean intrapatient number of fimH mutations (A) and the mean intrapatient logarithmic SSR (B). Solid thin lines at both sides of the straight line of correlation are the 95% confidence interval.

Fig 5

Fig 5

Correlation of E. coli adhesion capability and PCDAI. PCDAI was correlated to the mean intrapatient logarithmic percent adhesion value. Three-dimensional FimH protein representations above the straight line of correlation depicted FimH alleles mostly found within defined PCDAI ranges. FimH allele 2 was found within strains from patients with PCDAIs ranging from 30 to 37.5, while FimH allele 5 was found within strains from patients with PCDAIs ranging from 40 to 67.5. The dashed line depicts the cutoff adhesion value of 0.8%, as described in Materials and Methods.

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