The Arginine Deiminase Operon Is Responsible for a Fitness Trade-Off in Extended-Spectrum-β-Lactamase-Producing Strains of Escherichia coli

Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00635-19. doi: 10.1128/AAC.00635-19. Print 2019 Aug.


We previously identified an operon involved in an arginine deiminase (ADI) pathway (arc operon) on a CTX-M-producing plasmid from an O102-ST405 strain of Escherichia coli As the ADI pathway was shown to be involved in the virulence of various Gram-positive bacteria, we tested whether the ADI pathway could be involved in the epidemiological success of extended-spectrum-β-lactamase (ESBL)-producing E. coli strains. We studied two collections of human E. coli isolated in France (n = 493) and England (n = 1,509) and show that the prevalence of the arc operon (i) is higher in ESBL-producing strains (12.1%) than in nonproducers (2.5%), (ii) is higher in CTX-M-producing strains (16%) than in other ESBL producers (3.5%), and (iii) increased over time in ESBL-producing strains from 0% before 2000 to 43.3% in 2011 to 2012. The arc operon, found in strains from various phylogenetic backgrounds, is carried by IncF plasmids (85%) or chromosomes (15%) in regions framed by numerous insertion sequences, indicating multiple arrivals. Competition experiments showed that the arc operon enhances fitness of the strain in vitro in lysogeny broth with arginine. In vivo competition experiments showed that the arc operon is advantageous for the strain in a mouse model of urinary tract infection (UTI), whereas it is a burden in a mouse model of intestinal colonization. In summary, we have identified a trait linked to CTX-M-producing strains that is responsible for a trade-off between two main E. coli lifestyles, UTI and gut commensalism. This trait alone cannot explain the wide spread of ESBLs in E. coli but merits epidemiological surveillance.

Keywords: Escherichia coli; plasmids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • England
  • Escherichia coli / genetics*
  • Escherichia coli Infections / microbiology
  • France
  • Humans
  • Hydrolases / genetics*
  • Mice
  • Microbial Sensitivity Tests / methods
  • Operon / genetics*
  • Phylogeny
  • Plasmids / genetics
  • Urinary Tract Infections / microbiology
  • beta-Lactamases / genetics*


  • Hydrolases
  • beta-Lactamases
  • arginine deiminase