Characterizing carbapenemase-producing Escherichia coli isolates from Spain: high genetic heterogeneity and wide geographical spread

Front Cell Infect Microbiol. 2024 May 16:14:1390966. doi: 10.3389/fcimb.2024.1390966. eCollection 2024.

Abstract

Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure.

Methods: Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and whole-genome sequencing was performed. Antibiotic resistance and virulence-associated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed.

Results and discussion: The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were bla OXA-48 (45.6%), bla VIM-1 (23.3%), bla NDM-1 (7.8%), bla KPC-3 (6.7%), and bla NDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored bla NDM. Five of the plazomicin-resistant isolates harbored rmt. IncL plasmids were the most frequent (45.7%) and eight of these harbored bla VIM-1. bla OXA-48 was found in IncF plasmids in eight isolates. Metallo-β-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections.

Keywords: Escherichia coli; antibiotic resistance; carbapenemases; plasmids; sequence type; virulence factor genes; whole-genome sequencing.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Carbapenem-Resistant Enterobacteriaceae / classification
  • Carbapenem-Resistant Enterobacteriaceae / enzymology
  • Carbapenem-Resistant Enterobacteriaceae / genetics
  • Drug Resistance, Multiple, Bacterial / genetics
  • Escherichia coli Infections* / epidemiology
  • Escherichia coli Infections* / microbiology
  • Escherichia coli* / classification
  • Escherichia coli* / enzymology
  • Escherichia coli* / genetics
  • Genetic Heterogeneity*
  • Genotype
  • Humans
  • Microbial Sensitivity Tests
  • Phylogeny
  • Plasmids / genetics
  • Spain / epidemiology
  • Virulence Factors / genetics
  • beta-Lactamases* / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase
  • Virulence Factors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by CIBER—Consorcio Centro de Investigación Biomédica en Red (CIBERINFEC and CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; and by the Antibiotic Resistance Surveillance Programs of the National Center for Microbiology, Instituto de Salud Carlos III. This research was also supported by Personalized and precision medicine grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. Funded by NextGenerationEU funds from the European Union that finance the actions of the The Resilience and Recovery Facility.