Intensity and Mechanisms of Fluoroquinolone Resistance within theH30 andH30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli

Abstract

ABSTRACTThe recent expansion of theH30 subclone ofEscherichia colisequence type 131 (ST131) and its CTX-M-15-associatedH30Rx subset remains unexplained. Although ST131H30 typically exhibits fluoroquinolone resistance, so do multiple otherE. colilineages that have not expanded similarly. To determine whetherH30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistantE. coliisolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistantE. coliisolates (48 non-H30 and 41H30 [23H30Rx and 18H30 non-Rx]). We compared the MICs with theH30 andH30Rx status, the presence/number of nonsynonymous mutations ingyrA,parC, andparE, the presence ofaac(6′)-1b-cr(an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recentE. coliclinical isolates, ST131H30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-H30 isolates,H30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations ingyrA,parC, andparE(specificallygyrAD87N,parCE84V, andparEI529L), and a numerically higher prevalence of (H30Rx-associated)aac(6′)-1b-crbut lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [foraac(6′)-1b-cr: ciprofloxacin and norfloxacin only].parCD87N corresponded with ST131H30 andparEI529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131H30, especiallyH30Rx [ifaac(6′)-1b-crpositive], with subtle fitness advantages over other fluoroquinolone-resistantE. colistrains. This urges both parsimonious fluoroquinolone use and a search for other fitness-enhancing traits within ST131H30.