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 microgram/ml; norfloxacin MICs, 0.5 to 4 micrograms/ml; nalidixic acid MIC, 256 micrograms/ml were isolated from urinary tract infections (AlhR and OulR) during FQ therapy in immunocompromised patients infected by the parent FQ-susceptible strains (AlhS and OulS) (ciprofloxacin MICs, 0.032-0.063; norfloxacin MICs, 0.125-0.25; nalidixic acid MICs, 4-8) or from intestinal infection (GueR). Transformation of AlhR, OulR, and GueR by plasmid pJSW101 carrying the wild-type gyrA gene of Escherichia coli resulted in complementation (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 fragment identified a single point mutation leading to a substitution Ser-83 to Tyr in AlhR and to a substitution Ser-83 to Phe in OulR and in GueR. These results emphasize the potential risk of selection of FQ-resistant Salmonella during FQ therapy in immunocompromised patients and suggest that these strains differ from the parent strains at least by one mutation in the gyrA gene. They also confirm the role of substitutions in position 83 of gyrA in FQ-resistant clinical isolates of Salmonella.
Ouabdesselam
S
S
Centre Hospitalier Universitaire Henri Mondor, Créteil, France.
Tankovic
J
J
Soussy
C J
CJ
D000890:Anti-Infective Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000032:analysis; D004352:Drug Resistance, Microbial / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D024841:Fluoroquinolones; D005798:Genes, Bacterial / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000502:physiology*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012475:Salmonella / Q000187:drug effects*; D012480:Salmonella Infections / Q000382:microbiology*; D017422:Sequence Analysis, DNA
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones