Key evolutionary events in the emergence of a globally disseminated, carbapenem resistant clone in the Escherichia coli ST410 lineage

Yu Feng,Ke Ma,Lu Liu,Alan Mcnally,Zhiyong Zong,Yi Xie,Haiyan Long,Li Wei,Ji Lin

doi:10.1038/s42003-019-0569-1

Abstract

There is an urgent need to understand the global epidemiological landscape of carbapenem-resistant Escherichia coli (CREC). Here we provide combined genomic and phenotypic characterization of the emergence of a CREC clone from the ST410 lineage. We show that the clone expands with a single plasmid, within which there is frequent switching of the carbapenemase gene type between blaNDM and blaOXA-181 with no impact on plasmid stability or fitness. A search for clone-specific traits identified unique alleles of genes involved in adhesion and iron acquisition, which have been imported via recombination. These recombination-derived allelic switches had no impact on virulence in a simple infection model, but decreased efficiency in binding to abiotic surfaces and greatly enhanced fitness in iron limited conditions. Together our data show a footprint for evolution of a CREC clone, whereby recombination drives new alleles into the clone which provide a competitive advantage in colonizing mammalian hosts.

Highlights

There is an urgent need to understand the global epidemiological landscape of carbapenemresistant Escherichia coli (CREC)
Analysis of the ST167 and ST617 lineages showed some clear overlaps in evolutionary trajectory between these CREC clones and ST131 including mutations involved in host colonization and in intergenic regions associated with emergence of multi-drug resistant (MDR) plasmid-bearing clones[8], but there remains a need to determine if this pattern is common across emerging CREC clones
By using MinION sequencing in combination with the available Illumina genome data, we were able to show that the clone is dominated by an IncX3 plasmid which has expanded with the clone, but which frequently interchanges the carbapenemase genes blaNDM-5 and blaOXA-181 without any impact on plasmid stability or fitness

Summary

Introduction

There is an urgent need to understand the global epidemiological landscape of carbapenemresistant Escherichia coli (CREC). Escherichia coli, a member of the Enterobacteriaceae, is a major human pathogen causing various infections ranging from intestinal disease and urinary tract infections to invasive bloodstream infections Carbapenems such as ertapenem, imipenem, and meropenem are potent antimicrobial agents against the Enterobacteriaceae and have become the mainstream agents of choice to treat severe infections caused by E. coli. This lineage was similar to the global pandemic ESBL E. coli lineage ST131, in that a specific clone (B4/H24RxC) had arisen from the background population via acquisition of a resistance plasmid, in this instance the ST410 lineage containing an IncX3 plasmid carrying the blaOXA-181 carbapenemase gene[9].

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Results

Conclusion