Disease relevance of gyrA

• Clinical strains of Mycobacterium tuberculosis can be divided into three principal genetic groups based on the single-nucleotide polymorphisms at the katG gene codon 463 and the gyrA gene codon 95 [1].
• A C-8-bromo substituent also increased bacteriostatic and lethal activities against a gyrA mutant of M. bovis BCG [2].

High impact information on gyrA

• Sequencing of the corresponding regions revealed that, although the GyrA protein sequence was conserved, the nucleotide sequences differed in gyrA genes with and without inteins, suggesting that the homing endonuclease displays sequence specificity [3].
• The A subunit of DNA gyrase in Mycobacterium leprae, unlike its counterpart in Mycobacterium tuberculosis, is produced by protein splicing as its gene, gyrA, harbors a 1260-bp in-frame insertion encoding an intein, a putative homing endonuclease [3].
• In all four cases where intein coding sequences were found, they were localized in the same position in gyrA, immediately downstream of the codon for the key active-site residue Tyr-130 [3].
• Paired motifs, found in homing endonucleases encoded by some group I RNA introns, and inteins showing endonuclease activity, were present in the gyrA inteins as were other intein-specific signatures [3].
• The genetic profiles of the gyrA gene of the 138 isolates as detected by MPAC were confirmed by nucleotide sequencing and were found to correlate strongly with the in vitro susceptibilities of the mutant strains to six fluoroquinolones (ofloxacin, levofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, and sitafloxacin) [4].

Chemical compound and disease context of gyrA

• The C-8 methoxyl fluoroquinolone was also more effective than ciprofloxacin against a gyrA Asn94 mutant of M. bovis BCG [5].

Biological context of gyrA

• DNA-sequencing and single-strand conformation polymorphism (SSCP) were further utilized for characterization of the mutations in the QRDR of gyrA and gyrB genes and mutation screening, respectively [6].
• Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations [7].
• The two genes encoding DNA gyrase in Mycobacterium tuberculosis are present next to each other in the genome, with gyrB upstream of gyrA [8].
• The gyrA gene harbours an intein coding sequence indicating that protein splicing is required to produce the mature A subunit of DNA gyrase [9].
• The existence of these two families was also validated by an independent phylogenetic analysis of spoligotyping on a larger set of shared types (n = 252) and further corroborated by VNTR and katG-gyrA results [10].

Associations of gyrA with chemical compounds

• From DNA-sequencing, 21 of 35 (60%) exhibited single-point mutations in different positions, at Ala90Val, Ser91Pro, and Asp94(Gly/Ala/His/Asn); and one novel mutation position at Gly88Cys in the gyrA gene and Asp495Asn in the gyrB gene [6].
• Mutations in codons of gyrA analogous to those described in other FQ-resistant bacteria were identified in all isolates (n = 14) for which the ciprofloxacin MIC was > 2 micrograms/ml [7].
• A gyrA mutation in TKp1 secondary mutants was associated with 32- to 128-fold increases in the MICs of ofloxacin and ciprofloxacin compared with the MICs for H37Ra and an eight-fold increase in the MIC of sparfloxacin [11].
• Besides biochemical (sensitivity to pyrazinamide) and epidemiological features, strains of this unusual member of the M. tuberculosis complex show a special combination of pncA, oxyR, katG and gyrA gene polymorphisms [12].
• All gyrA mutations were clustered in codons 90, 91, and 94, and aspartic acid 94 was most frequently mutated [4].

Other interactions of gyrA

• Sequencing of the pncA gene revealed a polymorphism characteristic of M. tuberculosis, whereas oxyR, katG and gyrA sequences were characteristic of Mycobacterium bovis [13].

Analytical, diagnostic and therapeutic context of gyrA

• In this study, 35 isolates of FQr-MTB were collected from Siriraj Hospital and Chest Disease Institute. The quinolone-resistance-determining regions (QRDR) of gyrA and gyrB genes in all 35 FQr-MTB isolates and from the H37Ra MTB strain were amplified using polymerase chain reaction (PCR) [6].
• Molecular cloning of gyrA and gyrB genes of Mycobacterium tuberculosis: analysis of nucleotide sequence [14].
• Results were compared to sequence analysis of the gyrA gene and minimal inhibitory concentration determination [15].
• A single-strand conformation polymorphism (SSCP) methodology, based on the use of mini-gels and silver staining of DNA, was optimized for the analysis of denatured DNA products obtained by polymerase chain reaction (PCR) from the gyrA gene involved in fluoroquinolone resistance in mycobacteria [16].

References