Disease relevance of gyrA

• With E. coli, a gyrA, but not a parC, mutation raised the MIC of both compounds [1].
• Incidence of various gyrA mutants in 451 Staphylococcus aureus strains isolated in Japan and their susceptibilities to 10 fluoroquinolones [2].

High impact information on gyrA

• All first- and second-step mutants selected by WCK 771 revealed gyrA and grlA mutations, respectively [3].
• Our results demonstrate that gyrA is the primary target of WCK 771 and that it has pharmacodynamic properties remarkably different from those of quinolones with dual targets (garenoxacin and moxifloxacin) and topoisomerase IV-specific quinolones (trovafloxacin) [3].
• Species identification was confirmed by standard biochemical tests and analysis of 16S ribosomal DNA, gyrA, and gyrB sequences; all of the results were consistent with the S. aureus identification [4].
• There was no relationship between the time that ciprofloxacin concentrations remained between the MIC and the MPC and the degree of resistance or the presence or type of ciprofloxacin-resistance mutations that appeared in grlA or gyrA [5].
• The two- to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 x 10(-11) to 1.1 x 10(-10)), suggested similar targeting of the two enzymes by gemifloxacin [6].

Chemical compound and disease context of gyrA

• Detection of gyrA gene mutations associated with ciprofloxacin resistance in methicillin-resistant Staphylococcus aureus: analysis by polymerase chain reaction and automated direct DNA sequencing [7].
• A portion of the gyrA gene from amino acid codons 67 to 129 was sequenced in 34 methicillin-resistant Staphylococcus aureus strains (14 isolated in Minnesota, 10 isolated in Indiana, and 10 isolated in Tennessee) [7].
• The new 8-methoxyquinolone moxifloxacin was tested against two ciprofloxacin-susceptible Staphylococcus aureus strains (strains P8 and COL) and two ciprofloxacin-resistant derivatives of strain P8 carrying a single grlA mutation (strain P8-4) and double grlA and gyrA mutations (strain P8-128) [8].
• First, using Staphylococcus aureus strains containing point mutations in the serine 84-80 hot spots of the target genes (gyrA and grlA), cell growth inhibition potencies of the NFQs as a result of DNA gyrase and topoisomerase IV inhibition were estimated and compared with those of known fluoroquinolones [9].
• The antistaphylococcal activities of BMS-284756 (T-3811ME), levofloxacin, moxifloxacin, and ciprofloxacin were compared against wild-type and grlA and grlA/gyrA mutant strains of Staphylococcus aureus [10].

Biological context of gyrA

• The elimination of this plasmid from such quinolone-resistant gyrA mutants resulted in marked increases in quinolone susceptibility [11].
• A total of 36 clinical isolates of Staphylococcus aureus (29 fluoroquinolone-resistant strains and 7 fluoroquinolone-susceptible strains) were studied for the presence of point mutations in the gyrA gene by nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis with silver stain [12].
• Restriction fragment length polymorphism (RFLP) patterns around the gyrA gene in CNS were identical, but species specific, for all 10 MRSE and 10 MRSH isolates examined [13].
• A mutation of the gyrA gene resulting in an amino acid substitution was found in the second-step but not in the first-step resistant subclone [14].
• At saturating drug concentrations, norfloxacin and a gyrA mutant were used to show that topoisomerase IV-norfloxacin-cleaved DNA complexes are distributed on the S. aureus chromosome at intervals of about 30 kbp [15].

Associations of gyrA with chemical compounds

• With S. aureus, the dimer selected spontaneous resistant gyrA mutants, whereas ciprofloxacin selected a parC mutant [1].
• Using restriction fragment length polymorphism analysis and DNA sequencing, we found that in fluoroquinolone- and methicillin-resistant strains, mutations in grlA and gyrA are quite likely to be present together [16].
• All the sparfloxacin-resistant strains of MRSA tested contained the gyrA mutation at codon 84 [17].
• Double mutations in gyrA and grlA or grlB caused a 32-fold increase in the MIC of gatifloxacin, in contrast to a 128-fold increase for ciprofloxacin and AM-1121 [18].
• Finally, the gyrA (Leu-84) mutation previously described as silent for fluoroquinolone resistance increased the MIC of nalidixic acid, a nonfluorinated quinolone [19].

Regulatory relationships of gyrA

• The silent mutant allele of gyrA was present in a flqA background and expressed resistance only upon introduction of a grlA mutation [20].

Other interactions of gyrA

• Portions of the gyrA (codons 60 to 120) and the gyrB (codons 420 to 480) genes of each clinical isolate were amplified by PCR and sequenced [21].
• A double mutation (gyrA and either grlA or grlB) caused a 32-fold increase in the MIC of premafloxacin, while the MIC of ciprofloxacin increased 128-fold [22].
• Two genes previously associated with fluoroquinolone resistance, the gyrA gene of DNA gyrase and the norA gene (associated with decreased drug accumulation), were localized to the G and D fragments, respectively [23].
• For all target genes, the expression profiles obtained with gyrA or gmk as internal standards remained almost identical [24].

Analytical, diagnostic and therapeutic context of gyrA

• gyrA mutations in quinolone-resistant pathogenic isolates of Staphylococcus spp. have been detected by the direct HinfI digestion of polymerase chain reaction products [25].

References