Disease relevance of gyrA

• The fitness advantage was not due to compensatory mutations in the genes targeted by FQ and was linked directly to the single point mutation in gyrA, which confers on Campylobacter a high-level resistance to FQ antimicrobials [1].
• Consecutive isolates of quinolone-resistant campylobacter isolated over a 5 year period (1990-1995) from the faeces of patients with enteritis in Plymouth, UK, were examined for the epidemiology of mutations in gyrA (n = 127) [2].
• Distinct from other Gram-negative bacteria, the acquisition of FQ resistance in Campylobacter does not require stepwise accumulation of gyrA mutations and overexpression of efflux pumps, and is mainly mediated by single-step point mutations in gyrA in the presence of a constitutively expressed multidrug efflux pump, CmeABC [3].

High impact information on gyrA

• The replacement of the mutated gyrA with a wild-type gyrA allele resulted in a 32-fold decrease in the ciprofloxacin MIC and no change in the nalidixic acid MIC [4].
• Irrespective of the parent strain, mutants with the second phenotype were resistant to ciprofloxacin, chloramphenicol, tetracycline, ethidium bromide, acridine orange, and SDS and had no mutation in gyrA [5].
• Cloning and nucleotide sequencing of the C. fetus gyrA gene in the 2 resistant isolates demonstrated a G-to-T change that led to an Asp-to-Tyr amino acid substitution at a critical residue frequently associated with quinolone resistance [6].
• Cloning and nucleotide sequence of the gyrA gene from Campylobacter fetus subsp. fetus ATCC 27374 and characterization of ciprofloxacin-resistant laboratory and clinical isolates [7].
• In addition, clinical isolates and poultry isolates from Germany, The Netherlands and other regions of the UK collected before 1995 were examined for mutations in the quinolone resistance-determining region of gyrA by single-stranded conformational polymorphism analysis and direct sequencing of a 270 bp fragment of PCR-generated DNA [2].

Chemical compound and disease context of gyrA

• A novel gyrA sequence was amplified from two Campylobacter lari and one C. jejuni, which exhibited a valine at codon 86 [2].
• Two distinct mutations in gyrA lead to ciprofloxacin and nalidixic acid resistance in Campylobacter coli and Campylobacter jejuni isolated from chickens and beef cattle [8].

Biological context of gyrA

• The prolonged colonization in chickens did not result in loss of the FQ resistance and the resistance-conferring point mutation (C257 --> T) in the gyrA gene [1].
• The gyrA gene of Campylobacter fetus subsp. fetus, which encodes the A subunit of DNA gyrase, was cloned, and its nucleotide sequence was determined [7].
• While the quinolone resistance of strain PEFr could be explained by a mutation at codon 86 of the gyrA gene, the multidrug resistance phenotype of both strains was further investigated [9].
• A simple real-time fluorescence resonance energy transfer (FRET) PCR, targeting the gyrA gene outside the quinolone resistance-determining region, was developed to identify Campylobacter jejuni and Campylobacter coli [10].

Associations of gyrA with chemical compounds

• Resistance to 125 microgram of ciprofloxacin per ml in clinical isolates was associated with chromosomal mutations in C. jejuni leading to a Thr-86-Ile substitution in the gyrA product and a Arg-139-Gln substitution in the parC product [11].
• Mutation of gyrA at codon 86 (Thr-Ile) caused 128- and 64-fold increases in the MICs of ciprofloxacin and nalidixic acid, respectively [4].
• The range of susceptibility to erythromycin and kanamycin were typical of the species. gyrA from C. jejuni P6 (a case with history of travel to Spain) and C. jejuni P16 (isolate from imported chicken) contained point mutations corresponding to an amino acid substitution of isoleucine for threonine at codon 86 [12].
• First-step and second-step in vitro mutants, derived from reference strain C. coli ATCC 33559 with ciprofloxacin or moxifloxacin as selecting agents, were found to carry one and two mutations in gyrA, respectively [13].
• On the contrary, our results of study 2 demonstrated that administration of enrofloxacin generated a rapid increase of fluoroquinolone resistance in C. jejuni showing the mutation of Asp-90-Asn in the gyrA gene [14].

Other interactions of gyrA

• It carried a gyrA mutation leading to a Thr86-Ile substitution and was devoid of gyrB mutation [13].
• The usefulness of PCR fingerprinting of the gyrA/pflA genes for rapid ordering of strains by genotypic relatedness and providing additional information for estimating the degree of linkage between strains was demonstrated [15].

Analytical, diagnostic and therapeutic context of gyrA

• A mismatch amplification mutation assay (MAMA) PCR protocol was developed that detects this gyrA mutation in quinolone-resistant isolates [16].
• Representative ciprofloxacin-resistant mutants were selected for gyrA sequence analysis and MIC determination [17].

References