IDENTIFICATION OF MAR MUTANTS AMONG QUINOLONE-RESISTANT CLINICAL ISOLATES OF ESCHERICHIA-COLI

Quinolone-resistant clinical Escherichia coil isolates were examined f or mutations in the marRAB operon of the multiple antibiotic resistanc e (mar.) locus. Among 23 strains evaluated, 8 were chosen for further study: 3 that showed relatively high levels of uninduced, i.e., consti tutive, expression of the operon and 5 with variable responses to indu ction by salicylate or tetracyclines. The marR genes, specifying the r epressor of the operon, cloned from the three strains constitutively e xpressing the operon did not reduce the level of expression of beta-ga lactosidase from a marO::lacZ transcriptional fusion and were therefor e mutant; however, marR genes cloned from the five other clinical stra ins repressed LacZ expression and were wild type. All three mutant mar R genes contained more than one mutation: a deletion and a point mutat ion. Inactivation of the mar locus in the three known marR mutant stra ins with a kanamycin resistance cassette introduced by homologous reco mbination reduced resistance to quinolones and multiple antibiotics. T hese findings indicate that mar operon mutations exist in quinolone-re sistant clinical E. coli isolates and contribute to quinolone and mult idrug resistance.