Plasmid-Mediated Ciprofloxacin Resistance Imparts a Selective Advantage on Escherichia coli ST131

Escherichia coli ST131 is a recently emerged antibiotic resistant clone responsible for high rates of urinary tract and bloodstream infections. Despite its global dominance, the precise mechanisms that have driven the rapid dissemination of ST131 remain unknown. Here, we show that the plasmid-associated resistance gene encoding the AAC (6')-Ib-cr enzyme that inactivates the fluoroquinolone (FQ) antibiotic ciprofloxacin is present in >70% of strains from the most rapidly expanding subgroup of multidrug resistant ST131. Using a series of genome-edited and plasmid-cured isogenic strains, we demonstrate that the aac(6')-Ib-cr gene confers a selective advantage on ST131 in the presence of ciprofloxacin, even in strains containing chromosomal GyrA and ParC FQ-resistance mutations. Further, we identify a pattern of emerging carbapenem resistance in other common E. coli clones carrying both aac(6')-Ib-cr and chromosomal FQ-resistance mutations, suggesting this dual resistance combination may also impart a selective advantage on these non-ST131 antibiotic resistant lineages.

Automated summary

The plasmid-associated resistance gene, AAC (6')-Ib-cr, provides a selective advantage for the dissemination of Escherichia coli ST131, a highly antibiotic resistant clone. This gene, which inactivates the fluoroquinolone antibiotic ciprofloxacin, is present in over 70% of strains from the rapidly growing subgroup of multidrug resistant ST131. The presence of this gene gives ST131 an edge even in the presence of chromosomal FQ-resistance mutations.