Genomic Analysis of Factors Associated with Low Prevalence of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli Sequence Type 95 Strains.

Craig M Stephens,Lee W Riley,James R Johnson,Manraj Sekhon,Sheila Adams-Sapper,Brandi M Limbago

doi:10.1128/msphere.00390-16

Abstract

Extraintestinal pathogenic Escherichia coli (ExPEC) strains belonging to multilocus sequence type 95 (ST95) are globally distributed and a common cause of infections in humans and domestic fowl. ST95 isolates generally show a lower prevalence of acquired antimicrobial resistance than other pandemic ExPEC lineages. We took a genomic approach to identify factors that may underlie reduced resistance. We fully assembled genomes for four ST95 isolates representing the four major fimH-based lineages within ST95 and also analyzed draft-level genomes from another 82 ST95 isolates, largely from the western United States. The fully assembled genomes of antibiotic-resistant isolates carried resistance genes exclusively on large (>90-kb) IncFIB/IncFII plasmids. These replicons were common in the draft genomes as well, particularly in antibiotic-resistant isolates, but we also observed multiple instances of a smaller (8.3-kb) ampicillin resistance plasmid that had been previously identified in Salmonella enterica. Among ST95 isolates, pansusceptibility to antibiotics was significantly associated with the fimH6 lineage and the presence of homologs of the previously identified 114-kb IncFIB/IncFII plasmid pUTI89, both of which were also associated with reduced carriage of other plasmids. Potential mechanistic explanations for lineage- and plasmid-specific effects on the prevalence of antibiotic resistance within the ST95 group are discussed. IMPORTANCE Antibiotic resistance in bacterial pathogens is a major public health concern. This work was motivated by the observation that only a small proportion of ST95 isolates, a major pandemic lineage of extraintestinal pathogenic E.coli, have acquired antibiotic resistance, in contrast to many other pandemic lineages. Understanding bacterial genetic factors that may prevent acquisition of resistance could contribute to the development of new biological, medical, or public health strategies to reduce antibiotic-resistant infections.

Highlights

Extraintestinal pathogenic Escherichia coli (ExPEC) strains belonging to multilocus sequence type 95 (ST95) are globally distributed and a common cause of infections in humans and domestic fowl
A total of 53 E. coli ST95 isolates were subjected to whole-genome sequencing on the Illumina MiSeq platform, followed by de novo assembly and analysis (Table 1; see Table S1 in the supplemental material)
The fimH gene, which encodes an adhesin critical for urinary tract pathogenesis, has proven to be useful as a genetic marker to increase the resolution of multilocus sequence typing (MLST) with ExPEC strains [13, 14]

Summary

Introduction

Extraintestinal pathogenic Escherichia coli (ExPEC) strains belonging to multilocus sequence type 95 (ST95) are globally distributed and a common cause of infections in humans and domestic fowl. Diverse strains of the Gram-negative bacterium Escherichia coli are capable of causing many human illnesses, including both gastrointestinal and extraintestinal infections. This species is the most common cause of urinary tract infections (UTIs) [1] and a leading cause of bloodstream infections (BSIs) [2]. Adams-Sapper et al [6] noted that, at least in San Francisco, the fimH6 sublineage of the ST95 group was nearly always pansusceptible and yet very common This implies, first, that antimicrobial resistance may not be a major factor contributing to the pandemicity of ST95 strains, and second, that there may be something distinctive about fimH6 strains with respect to acquisition or maintenance of antibiotic resistance

Methods

Results

Conclusion