QUINOLONE RESISTANCE MUTATIONS IN THE GYRA GENE OF CLINICAL ISOLATES OF SALMONELLA

S. typhimurium AlhR, S. enteritidis OulR, and S. hadar GueR resistant to fluoroquinolones (QR), ciprofloxacin MICs, 0.25 to 1 mu g/ml; norfl oxacin MICs, 0.5 to 4 mu g/ml; nalidixic acid MIG, 256 mu g/ml were is olated from urinary tract infections (AlhR and OulR) during FQ therapy in immunocompromised patients infected by the parent FQ-susceptible s trains (AlhS and OulS) (ciprofloxacin MICs, 0.032-0.063; norfloxacin M ICs, 0.125-0.25; nalidixic acid MICs, 4-8) or from intestinal infectio n (GueR). Transformation of AlhR, OulR, and GueR by plasmid pJSW101 ca rrying the wild-type gyrA gene of Escherichia coli resulted in complem entation (nalidixic acid MICs, 4 to 8), proving that these strains had a gyrA mutation. A 800-bp fragment of gyrA from the five strains was amplified by PCR. Direct DNA sequencing of 252-bp region of this fragm ent identified a single point mutation leading to a substitution Ser-8 3 to Tyr in AlhR and to a substitution Ser-83 to Phe in OulR and in Gu eR. These results emphasize the potential risk of selection of FQ-resi stant Salmonella during FQ therapy in immunocompromised patients and s uggest that these strains differ from the parent strains at least by o ne mutation in the gyrA gene. They also confirm the role of substituti ons in position 83 of gyrA in FQ-resistant clinical isolates of Salmon ella.