Extraintestinal Virulence Is a Coincidental By-Product of Commensalism in B2 Phylogenetic Group Escherichia coli Strains

Abstract

The selective pressures leading to the evolution and maintenance of virulence in the case of facultative pathogens are quite unclear. For example, Escherichia coli, a commensal of the gut of warm-blooded animals and humans, can cause severe extraintestinal diseases, such as septicemia and meningitis, which represent evolutionary dead ends for the pathogen as they are associated to rapid host death and poor interhost transmission. Such infectious process has been linked to the presence of so-called "virulence genes." To understand the evolutionary forces that select and maintain these genes, we focused our study on E. coli B2 phylogenetic group strains that encompass both commensal and pathogenic (extra- and intraintestinal) strains. Multilocus sequence typing (MLST), comparative genomic hybridization of the B2 flexible gene pool, and quantification of extraintestinal virulence using a mouse model of septicemia were performed on a panel of 60 B2 strains chosen for their genetic and ecologic diversity. The phylogenetic history of the strains reconstructed from the MLST data indicates the emergence of at least 9 subgroups of strains. A high polymorphism is observed in the B2 flexible gene pool among the strains with a good correlation between the MLST-inferred phylogenetic history of the strains and the presence/absence of specific genomic regions, indicating coevolution between the chromosomal background and the flexible gene pool. Virulence in the mouse model is a highly prevalent and widespread character present in all subgroups except one. Association studies reveal that extraintestinal virulence is a multigenic process with a common set of "virulence determinants" encompassing genes involved in transcriptional regulation, iron metabolism, adhesion, lipopolysaccharide (LPS) biosynthesis, and the recently reported peptide polyketide hybrid synthesis system. Interestingly, these determinants can also be viewed as intestinal colonization and survival factors linked to commensalism as they can increase the fitness of the strains within the normal gut environment. Altogether, these data argue for an ancestral emergence of the extraintestinal virulence character that is a coincidental by-product of commensalism. Furthermore, the phenotypic and genotypic markers identified in this work will allow further epidemiological studies devoted to test the niche specialization hypothesis for the B2 phylogenetic subgroups.

Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains

“…We found that isolates with the greatest content of VF genes were associated with the highest mortality. Interestingly, even a rectal isolate was capable of very high mortality, in agreement with the notion that virulence is a by-product of commensalism [24] (Fig. 3a).…”

“…The distribution pattern was similar among sites, although there was a trend towards a higher proportion of B2 in the respiratory tract than in the oropharyngeal and the rectal site (66, 51, and 49 %, respectively) sfa was screened in 18 pneumonia and 8 colonization isolates, and cnf1 was screened in 13 pneumonia and 6 colonization isolates UG ungrouped, NT non O1, O2a, O4, O6a, O7, O12, O15, O16, O18, O25a, O75, O157 a Determined by the triplex PCR method of Clermont et al [19] b According to Ref. [24] c Sequence type complex (STc) according to the Achtman multilocus sequence typing (MLST) scheme (http://mlst.ucc.ie) d According to Ref. [23] e The virulence genes were grouped in pathogenicity islands (PAIs) and plasmid as in Ref.…”

“…VAP B2 phylogroup isolates were further characterized by presence of 11 additional VF [20], PCR O-typing [23], and B2-subgrouping [24].…”

Molecular Epidemiology and Phylogenetic Distribution of the Escherichia coli pks Genomic Island

“…Many strains belonging to this phylogenetic group cause extraintestinal infections, such as urinary tract infections and septicemia. Colibactin can thus be regarded as a VF of ExPEC, but little is known about its prevalence among isolates from defined clinical syndromes versus commensal strains or its associations with other VFs (13,16,25). In addition, certain commensal strains from healthy people also possess the pks island (13).…”

“…Colibactin can thus be regarded as a VF of ExPEC, but little is known about its prevalence among isolates from defined clinical syndromes versus commensal strains or its associations with other VFs (13,16,25). In addition, certain commensal strains from healthy people also possess the pks island (13). Of note, one such commensal, the probiotic strain Nissle 1917, contains the pks island and produces a functional genotoxin (16).…”