Disease relevance of grlA

• A 4.6 kb Staphylococcus aureus DNA fragment containing DNA gyrase-like genes (grlA and grlB) was cloned and sequenced [1].

High impact information on grlA

• There was no relationship between the time concentrations remained between the MIC and the MPC and the degree of resistance or the presence or type of mutations that appeared in grlA/B or gyrA [2].
• The enrichment of subpopulations with mutations in grlA and low-level ciprofloxacin resistance also varied depending on the pharmacokinetic environment [3].
• Selection of novel resistance mutations in grlA requires further expansion of quinolone-resistance-determining regions, and their study may provide increased insight into enzyme-quinolone interactions [4].
• Both the wild-type strain MT5 and grlA mutant MT5224c4 should be considered susceptible to both BMS-284756 and levofloxacin, and both quinolones are predicted to have clinical efficacy [5].
• Exposure of this mutant to norfloxacin produced SA K1748, a derivative with raised fluoroquinolone MICs, found to be the result of a grlA mutation, and raised organic cation MICs [6].

Chemical compound and disease context of grlA

• Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus [7].
• Association of mutations in grlA and gyrA topoisomerase genes with resistance to ciprofloxacin in epidemic and sporadic isolates of methicillin-resistant Staphylococcus aureus [8].
• Activities of trovafloxacin compared with those of other fluoroquinolones against purified topoisomerases and gyrA and grlA mutants of Staphylococcus aureus [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 [5].
• 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 [10].

Biological context of grlA

• The presence of wild-type grlB-grlA gene sequences in second-step mutants excluded involvement of topoisomerase IV in the small-colony phenotype [11].
• The grlA point mutations of CAT-->CAC (His-77 [silent]), TCA-->CCA (Ser-81-->Pro), and ATA-->ATT (Ile-100 [silent]) were novel, as was the GAC-->GGC (Asp-73-->Gly) change in gyrA [12].
• However, dominance by mutated grlA genes depended on gene dosage when bacteria were transformed with the grlA and grlB genes in combination [13].
• Increased bacterial adhesion of the highly quinolone-resistant mutants, which contained combined mutations in grlA and gyrA, was associated with and explained by the overexpression of their fibronectin-binding proteins as assessed by Western ligand affinity blotting [14].
• Quinolone-resistant gyrA mutants were easily isolated from a strain, S. aureus RN4220, carrying a plasmid with the mutated grlA gene, though this was not the case for other S. aureus strains lacking the plasmid [13].

Associations of grlA with chemical compounds

• For fluoroquinolone-resistant but methicillin-susceptible strains, mutations in grlA alone are more common [15].
• Those properties of gatifloxacin likely explain its good activity against quinolone-resistant clinical isolates of S. aureus harboring the grlA, gyrA, and/or norA mutations [16].
• Second-step mutants were found to have, in addition to a mutation in grlA, reduced accumulation of norfloxacin or an alteration in GyrA at Ser-84 to Leu or Glu-88 to Lys [7].
• For mutants with changes in both grlA and gyrA MICs were higher and were generally above the susceptibility breakpoint for ciprofloxacin, sparfloxacin, levofloxacin, and pefloxacin [9].
• Ofloxacin and trovafloxacin selected most commonly for mutations in grlA, conferring substitutions for Ser-80 [17].

Regulatory relationships of grlA

• The silent mutant allele of gyrA was present in a flqA background and expressed resistance only upon introduction of a grlA mutation [18].

Analytical, diagnostic and therapeutic context of grlA

• Real-time PCR assay for detection of fluoroquinolone resistance associated with grlA mutations in Staphylococcus aureus [19].

References