Whole genome sequencing of uropathogenic E. coli from Ireland reveals diverse resistance mechanisms and strong correlation with phenotypic (EUCAST) susceptibility testing

Infect Genet Evol. 2024 Jul:121:105600. doi: 10.1016/j.meegid.2024.105600. Epub 2024 Apr 29.

Abstract

Urinary tract infections (UTI) caused by uropathogenic Escherichia coli (UPEC) pose a global health concern. Resistance mechanisms, including genetic mutations in antimicrobial target genes, efflux pumps, and drug deactivating enzymes, hinder clinical treatment. These resistance factors often spread through mobile genetic elements. Molecular techniques like whole genome sequencing (WGS), multilocus sequence typing (MLST), and phylotyping help decode bacterial genomes and categorise resistance genes. In this study, we analysed 57 UPEC isolates from different UTI patients following EUCAST guidelines. A selection of 17 representative strains underwent WGS, phylotyping, MLST, and comparative analysis to connect laboratory susceptibility data with predictive genomics based on key resistance genes and chromosomal mutations in antimicrobial targets. Trimethoprim resistance consistently correlated with dfr genes, with six different alleles detected among the isolates. These dfr genes often coexisted with class 1 integrons, with the most common gene cassette combining dfr and aadA. Furthermore, 52.9% of isolates harboured the blaTem-1 gene, rendering resistance to ampicillin and amoxicillin. Ciprofloxacin-resistant strains exhibited mutations in GyrA, GyrB and ParC, plasmid-mediated quinolone resistance genes (qnrb10), and aac(6')-Ib-cr5. Nitrofurantoin resistance in one isolate stemmed from a four amino acid deletion in NfsB. These findings illustrate the varied strategies employed by UPEC to resist antibiotics and the correlation between clinical susceptibility testing and molecular determinants. As molecular testing gains prominence in clinical applications, understanding key resistance determinants becomes crucial for accurate susceptibility testing and guiding effective antimicrobial therapy.

Keywords: Antibiotic resistance; Mobile genetic elements; Urinary tract infections; Uropathogenic E. coli; Whole genome sequencing.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Drug Resistance, Bacterial / genetics
  • Escherichia coli Infections* / microbiology
  • Female
  • Genome, Bacterial
  • Humans
  • Ireland
  • Male
  • Microbial Sensitivity Tests*
  • Multilocus Sequence Typing
  • Phenotype
  • Phylogeny
  • Urinary Tract Infections* / microbiology
  • Uropathogenic Escherichia coli* / drug effects
  • Uropathogenic Escherichia coli* / genetics
  • Whole Genome Sequencing* / methods

Substances

  • Anti-Bacterial Agents