Role of Homologous Recombination in Adaptive Diversification of Extraintestinal Escherichia coli

Abstract

The contribution of homologous exchange (recombination) of core genes in the adaptive evolution of bacterial pathogens is not well understood. To investigate this, we analyzed fully assembled genomes of two Escherichia coli strains from sequence type 131 (ST131), a clonal group that is both the leading cause of extraintestinal E. coli infections and the main source of fluoroquinolone-resistant E. coli. Although the sequences of each of the seven multilocus sequence typing genes were identical in the two ST131 isolates, the strains diverged from one another by homologous recombination that affected at least 9% of core genes. This was on a par with the contribution to genomic diversity of horizontal gene transfer and point gene mutation. The genomic positions of recombinant and mobile genetic regions were partially linked, suggesting their concurrent occurrence. One of the genes affected by homologous recombination was fimH, which encodes mannose-specific type 1 fimbrial adhesin, resulting in functionally distinct copies of the gene in ST131 strains. One strain, a uropathogenic isolate, had a pathoadaptive variant of fimH that was acquired by homologous replacement into the commensal strain background. Close examination of FimH structure and function in additional ST131 isolates revealed that recombination led to acquisition of several functionally distinct variants that, upon homologous exchange, were targeted by a variety of pathoadaptive mutations under strong positive selection. Different recombinant fimH strains also showed a strong clonal association with ST131 isolates that had distinct fluoroquinolone resistance profiles. Thus, homologous recombination of core genes plays a significant role in adaptive diversification of bacterial pathogens, especially at the level of clonally related groups of isolates.

Genomic and Functional Portrait of a Highly Virulent, CTX-M-15-Producing H 30-Rx Subclone of Escherichia coli Sequence Type 131

“…Our data lend support to observations indicating adaptive diversification and clonal expansion of ST131 as the underlying mechanisms for the evolution of fluoroquinolone-resistant and ESBL-producing ST131 E. coli (44,45). Our data also reveal that the similarity in phenotypes observed for our two ST131 strains correlates with the observation of the clonal genetic structure due to the evolution of a distinct subclade within ST131, namely, H30-Rx (10).…”

Predictive Diagnostics for Escherichia coli Infections Based on the Clonal Association of Antimicrobial Resistance and Clinical Outcome

“…qPCR was performed on LightCycler 2.0 (Hoffmann-La Roche, Inc.) using gene-or single-nucleotide polymorphism (SNP)-based primers specific to the clonotype CH40-30 (also known as H30). The gene-based probes targeted the rMST1 gene region described earlier (7). Pyrosequencing was performed on PyroMark Q24 (Qiagen, Inc.), targeting the short most-clonotype-variable (Ͻ60 bp) internal regions of fimH and fumC.…”

Global dissemination of a multidrug resistant Escherichia coli clone

“…Here, we have used genome sequencing to map the temporal and spatial relationship of a large collection of E. coli ST131 strains isolated from six distinct geographical regions across the world. We show that E. coli ST131 strains are distinct from other extraintestinal pathogenic E. coli and arose from a single progenitor strain prior to the year 2000. is also common to other strains in the FimH30 subgroup (23) and colonizes the mouse bladder in a type 1 fimbriae-dependent manner (15). In mice, E. coli EC958 establishes acute and chronic urinary tract infection (UTI), forms intracellular bacterial communities in the bladder (24), and causes impairment of ureter contractility (25).…”