| Accession | ARO:3003295 |
| Synonym(s) | Rv0006 |
| CARD Short Name | Mtub_gyrA_FLO |
| Definition | Point mutation of Mycobacterium tuberculosis gyrA resulted in the lowered affinity between fluoroquinolones and gyrA. Thus, conferring resistance. |
| AMR Gene Family | fluoroquinolone resistant gyrA |
| Drug Class | fluoroquinolone antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Mycobacterium aviumg, Mycobacterium tuberculosisg+wgs |
| Classification | 11 ontology terms | Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + determinant of antibiotic resistance + antibiotic resistant gene variant or mutant + antibiotic resistant DNA topoisomerase subunit + antibiotic molecule + fluoroquinolone resistant DNA topoisomerase + antibiotic resistant DNA topoisomerase subunit gyrA + fluoroquinolone antibiotic [Drug Class] |
| Parent Term(s) | 14 ontology terms | Show + confers_resistance_to_antibiotic enoxacin [Antibiotic] + confers_resistance_to_antibiotic ciprofloxacin [Antibiotic] + confers_resistance_to_antibiotic levofloxacin [Antibiotic] + confers_resistance_to_antibiotic moxifloxacin [Antibiotic] + confers_resistance_to_antibiotic gatifloxacin [Antibiotic] + confers_resistance_to_antibiotic lomefloxacin [Antibiotic] + confers_resistance_to_antibiotic nalidixic acid [Antibiotic] + confers_resistance_to_antibiotic norfloxacin [Antibiotic] + confers_resistance_to_antibiotic ofloxacin [Antibiotic] + confers_resistance_to_antibiotic trovafloxacin [Antibiotic] + confers_resistance_to_antibiotic grepafloxacin [Antibiotic] + confers_resistance_to_antibiotic sparfloxacin [Antibiotic] + confers_resistance_to_antibiotic pefloxacin [Antibiotic] + fluoroquinolone resistant gyrA [AMR Gene Family] |
| Publications | Campbell PJ, et al. 2011. Antimicrob Agents Chemother 55(5): 2032-2041. Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. (PMID 21300839) Takiff HE, et al. 1994. Antimicrob. Agents Chemother. 38(4):773-80 Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. (PMID 8031045) Shi R, et al. 2006. J. Clin. Microbiol. 44(12):4566-8 Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing. (PMID 17035499) Aubry A, et al. 2006. Antimicrob. Agents Chemother. 50(1):104-12 Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis: functional analysis of mutant enzymes. (PMID 16377674) Matrat S, et al. 2006. Antimicrob. Agents Chemother. 50(12):4170-3 Functional analysis of DNA gyrase mutant enzymes carrying mutations at position 88 in the A subunit found in clinical strains of Mycobacterium tuberculosis resistant to fluoroquinolones. (PMID 17015625) Von Groll A, et al. 2009. Antimicrob. Agents Chemother. 53(10):4498-500 Fluoroquinolone resistance in Mycobacterium tuberculosis and mutations in gyrA and gyrB. (PMID 19687244) Sulochana S, et al. 2007. J Chemother 19(2):166-71 Analysis of fluoroquinolone resistance in clinical isolates of Mycobacterium tuberculosis from India. (PMID 17434825) Kam KM, et al. 2006. Microb. Drug Resist. 12(1):7-11 Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of multidrug-resistant Mycobacterium tuberculosis: correlation with ofloxacin susceptibility. (PMID 16584301) Arjomandzadegan M, et al. 2016. Int J Mycobacteriol 5(3):299-305 Molecular detection of fluoroquinolone resistance-associated gyrA mutations in ofloxacin-resistant clinical isolates of Mycobacterium tuberculosis from Iran and Belarus. (PMID 27847014) Ezewudo M, et al. 2018. Sci Rep 8(1):15382 Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase. (PMID 30337678) The CRyPTIC Consortium 2022. PLoS Biol 20(8):e3001721 A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics. (PMID 35944069) World Health Organization. 2023. ISBN 978-92-4-008241-0. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Second Edition. (ISBN 978-92-4-008241-0) |
Prevalence of Mycobacterium tuberculosis gyrA conferring resistance to fluoroquinolones among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 414 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI | GRDI-AMR2 |
|---|---|---|---|---|---|
| Mycobacterium avium | 2.44% | 0% | 0% | 0% | 0% |
| Mycobacterium tuberculosis | 23.36% | 0% | 15.41% | 0% | 0% |
Model Type: protein variant model
Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.
Bit-score Cut-off (blastP): 1500
PubMed: mutation data hand curated from the scientific literature, evaluated as conferring resistance (R). CRyPTIC: mutation data acquired from the CRyPTIC catalog, evaluated as resistant (R), susceptible (S), or undetermined (U). ReSeqTB: mutation data acquired from the ReSeqTB catalog, evaluated as conferring resistance (Minimal, Moderate, High), not conferring resistance (None), or Indeterminate. WHO: mutation data acquired from the WHO 2023 catalog, evaluated as resistant (R), susceptible (S), or undetermined (U).| Mutation | Mutation type | PubMed | ReSeqTB | CRyPTIC | WHO |
|---|---|---|---|---|---|
| A74S | single resistance variant | PMID:17035499 | no data | no data | WHO-U |
| T80A | single resistance variant | PMID:16377674 | no data | CRyPTIC-S | WHO-S |
| G88A | single resistance variant | PMID:21300839 | no data | CRyPTIC-R | WHO-R |
| G88C | single resistance variant | PMID:21300839 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| D89V | single resistance variant | PMID:21300839 | no data | no data | no data |
| D89N | single resistance variant | PMID:21300839 | ReSeqTB-High | CRyPTIC-U | WHO-R |
| D89G | single resistance variant | PMID:21300839 | no data | no data | WHO-U |
| A90V | single resistance variant | PMID:21300839 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| A90G | single resistance variant | PMID:21300839 | no data | no data | WHO-S |
| A90V,D94G | multiple resistance variants | PMID:16377674 | no data | no data | no data |
| S91P | single resistance variant | PMID:21300839 | ReSeqTB-Moderate | CRyPTIC-R | WHO-R |
| D94Y | single resistance variant | PMID:21300839 | no data | CRyPTIC-R | WHO-R |
| D94V | single resistance variant | PMID:21300839 | no data | no data | WHO-U |
| D94H | single resistance variant | no data | ReSeqTB-High | CRyPTIC-R | WHO-R |
| D94A | single resistance variant | PMID:21300839 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| D94G | single resistance variant | PMID:21300839 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| D94N | single resistance variant | PMID:21300839 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| D94T | single resistance variant | PMID:27847014 | no data | no data | no data |
| P102H | single resistance variant | PMID:16584301 | no data | no data | no data |
| 39879,G247S+40052,D500N | co-dependent single resistance variant | PMID:21300839 | no data | no data | no data |
| 39879,A90V+40052,D472H | co-dependent single resistance variant | PMID:16377674 | no data | no data | no data |
| Curator | Description | Most Recent Edit |
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