Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Moxifloxacin-resistant mutants of Brucella melitensis 16M [moxifloxacin minimum inhibitory concentration (MIC)=1mg/L] were selected in order to characterise fluoroquinolone resistance mechanisms in this species. Eight independent mutants were obtained, with moxifloxacin MICs of 16-32mg/L. The mutants displayed variable cross-resistance levels to other fluoroquinolone compounds, but no increased resistance to aminoglycosides, tetracycline, rifampicin, macrolides or co-trimoxazole. Sequencing of type II topoisomerase-encoding genes (gyrA, gyrB, parC and parE), which are natural targets for fluoroquinolones, revealed a gyrA mutation leading to the amino acid substitution Ala83Val (Escherichia coli numbering system) in five mutants with a moxifloxacin MIC of 32mg/L, whereas no mutation was found in the remaining three mutants with a MIC of 16mg/L. Phenylalanine-arginine-beta-naphthylamide dihydrochloride, an efflux pump inhibitor, reduced moxifloxacin MICs by a factor of two to eight in all resistant mutants. In B. melitensis, fluoroquinolone resistance may arise from gyrA mutation and efflux pump overexpression mechanisms.
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PMID:In vitro selection of fluoroquinolone resistance in Brucella melitensis. 1926 48

A total of 171 Salmonella enterica serovar Typhi strains isolated from Nepal, mostly from patients with typhoid fever in 2002-2003, were tested for antimicrobial susceptibility by disk diffusion assay. Selected S. enterica serovar Typhi isolates were tested for MICs by E-test for ceftriaxone, ciprofloxacin and ofloxacin. Mutations of DNA gyrase gyrA and gyrB and topoisomerase IV parC and parE were identified by sequencing of PCR amplicons. By disk diffusion assay, 75/171 S. enterica serovar Typhi isolates were resistant to nalidixic acid, ampicillin, choramphenicol, streptomycin, tetracycline, sulfisoxazole, and trimethroprim/sulfamethoxazoles. Multiple drug resistance to the 7 antimicrobials was most predominant among S. enterica serovar Typhi isolates in this study. Resistance to nalidixic acid was detected in 76/111 and 56/60 of total isolates collected in 2002 and 2003, respectively. Nalidixic acid-resistant isolates in 2002 and 2003 showed MIC range for ciprofloxacin of 0.125-0.250 mg/l. Nalidixic acid-resistant isolates contained point mutations in gyrA and parC but not gyrB and parE. The gyrA mutation of nalidixic acid-resistant isolates obtained in 2002 and 2003 had amino acid substitution at position 83 of Serine-->Tyrosine and Serine-->Phenylalanine, respectively. Two different mutations of gyrA were detected among nalidixic acid-resistant isolates. Thus it is necessary to monitor mutation in DNA topoisomerase associated with increases in quinolones resistance.
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PMID:Emergence and properties of fluoroquinolone resistant Salmonella enterica serovar Typhi strains isolated from Nepal in 2002 and 2003. 2132 18