The link between phylogeny and virulence in Escherichia coli extraintestinal infection

Abstract

Previous studies suggesting a link between Escherichia coli phylogenetic groups and extraintestinal virulence have been hampered by the difficulty in establishing the intrinsic virulence of a bacterial strain. Indeed, unidentified virulence factors do exist, and the susceptibility of the host to infection is highly variable. To overcome these difficulties, we have developed a mouse model of extraintestinal virulence to test the virulence of the strains under normalized conditions. We then assessed the phylogenetic relationships compared to the E. coli reference (ECOR) collection, the presence of several known virulence determinants, and the lethality to mice of 82 human adult E. coli strains isolated from normal feces and during the course of extraintestinal infections. Commensal strains belong mainly to phylogenetic groups A and B1, are devoid of virulence determinants, and do not kill the mice. Strains exhibiting the same characteristics as the commensal strains can be isolated under pathogenic conditions, thus indicating the role of host-dependent factors, such as susceptibility linked to underlying disease, in the development of infection. Some strains of phylogenetic groups A, B1, and D are able to kill the mice, their virulence being most often correlated with the presence of virulence determinants. Lastly, strains of the B2 phylogenetic group represent a divergent lineage of highly virulent strains which kill the mice at high frequency and possess the highest level of virulence determinants. The observed link between virulence and phylogeny could correspond to the necessity of virulence determinants in a genetic background that is adequate for the emergence of a virulent clone, an expression of the interdependency of pathogenicity and metabolic activities in pathogenic bacteria.

FIG. 1

Factorial analysis of correspondence of the 72 strains of the ECOR collection (+) based on the rrn RFLP data (9). The 82 E. coli clinical isolates belonging to groups 1 (▴), 2 (■), 3 (▾), 4 (▵), 5 (□), and 6 (▿), considered supplementary observations, are projected in the F1/F2 plane. This plane, obtained by computation, is defined by the two principal axes of the analysis; the first axis, F1, explains most of the variance, and the second axis, F2 (orthogonal to F1), explains most of the variance which is not explained by F1. Phylogenetic groups A, B1, B2, and D (17) of E. coli are indicated. For clarity, when several strains are projected on the same point, only one is represented.

FIG. 2

Graphical representation of the results of the FAC carried out with the whole data from the 82 E. coli clinical strains. (A) Projections of the variables on the F1/F2 plane (defined as in Fig. 1): hly, detection of the hly operon; aer, detection of the aer operon; sfa, detection of the sfa/foc operon; ibe, detection of the ibe10 gene; pap, detection of the pap operon, afa, detection of the afa operon; K1, detection of the K1 antigen; b1, carboxylesterase B type B₁; b2, carboxylesterase B type B₂; B2, phylogenetic group B2; B1, phylogenetic group B1; A, phylogenetic group A; D, phylogenetic group D; pat, pathologic origin; co, commensal origin; 0/1, low level of lethality to mice; 2/8, medium level of lethality to mice; 9/10, high level of lethality to mice. The + and − signs after the variables indicate the presence or absence of the variable, respectively. (B) Projections of the 82 E. coli strains on the F1/F3 plane. The third axis F3, orthogonal to the F1/F2 plane, explains the largest part of the variance which is not explained by the F1/F2 plane. The strains (▴) are numbered as in Table 1, and for clarity, when several strains are projected on the same point, only one is represented.