Association between double mutation in gyrA gene of ciprofloxacin-resistant clinical isolates of Escherichia coli and MICs.
The mutations in the quinolone resistance-determining region of the gyrA and gyrB genes from 27 clinical isolates of Escherichia coli with a range of MICs of ciprofloxacin from 0.007 to 128 micrograms/ml and of nalidixic acid from 2 to > 2,000 micrograms/ml were determined by DNA sequencing. All 15 isolates with ciprofloxacin MICs of > or = 1 micrograms/ml showed a change in Ser-83 to Leu of GyrA protein, whereas in clinical isolates with a MIC of > or = 8 micrograms/ml (11 strains), a double change in Ser-83 and Asp-87 was found. All isolates with a MIC of nalidixic acid of > or = 128 micrograms/ml showed a mutation at amino acid codon Ser-83. Only 1 of the 27 clinical isolates of E. coli analyzed showed a change in Lys-447 of the B subunit of DNA gyrase. A change in Ser-83 is sufficient to generate a high level of resistance to nalidixic acid, whereas a second mutation at Asp-87 in the A subunit of DNA gyrase may play a complementary role in developing the strain's high levels of ciprofloxacin resistance.
Hospital Clínic, Departament de Microbiologia, Facultat de Medicina, Universitat de Barcelona, Spain.
J
J
Vila
J
J
Ruiz
F
F
Marco
A
A
Barcelo
P
P
Goñi
E
E
Giralt
T
T
Jimenez de Anta
D000595:Amino Acid Sequence; D001483:Base Sequence; D002939:Ciprofloxacin / Q000494:pharmacology*; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation
D002939:Ciprofloxacin; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II