The Arginine Deiminase Operon Is Responsible for a Fitness Trade-Off in Extended-Spectrum-β-Lactamase-Producing Strains ofEscherichia coli
ABSTRACTWe previously identified an operon involved in an arginine deiminase (ADI) pathway (arcoperon) on a CTX-M-producing plasmid from an O102-ST405 strain ofEscherichia 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)-producingE. colistrains. We studied two collections of humanE. coliisolated in France (n = 493) and England (n = 1,509) and show that the prevalence of thearcoperon (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. Thearcoperon, 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 thearcoperon enhances fitness of the strainin vitroin lysogeny broth with arginine.In vivocompetition experiments showed that thearcoperon 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 mainE. colilifestyles, UTI and gut commensalism. This trait alone cannot explain the wide spread of ESBLs inE. colibut merits epidemiological surveillance.