Prevalence and phylogenetic history of the TcpC virulence determinant in Escherichia coli

Abstract

Extraintestinal pathogenic Escherichia coli (ExPECs) possess an armament of virulence factors to colonize and infect the host, such as adhesins, toxins, capsules and iron-uptake systems. Recently, we could identify a novel virulence factor of ExPECs that interferes with the innate immune response of the host by interrupting the NF-κB signaling pathway. This protein named TcpC shows considerable homology to motifs of the Tir domain of Toll-like receptors. Here we demonstrate that the tcpC gene is widely distributed among clinical ExPEC isolates with almost half of the E. coli strains from patients suffering pyelonephritis shown to be tcpC positive as compared to only 8% in commensal isolates. However, this gene is only present in phylogenetic group B2 strains. Interestingly, the tcpC gene is strongly associated with presence of the high-pathogenicity island (HPI). The phylogenetic history of the tcpC gene, in the E. coli reference collection (ECOR) and other well-defined E. coli strains, compared to the phylogenetic histories of the HPI and the strains, showed that the tcpC gene (i) is scattered among various B2 subgroups with specific O-types, (ii) has a phylogeny incongruent with the strain phylogeny, but (iii) congruent with the HPI phylogenetic history. This, together with the strong conservation of the tcpC gene, indicates a very recent introduction of this virulence factor into E. coli by horizontal gene transfer which occurred “en bloc” with the HPI at one major hot spot of recombination in the E. coli genome. The present data provide evidence for a strong impact of homologous recombination events in the spread of the TcpC virulence trait among E. coli.