Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolone

Accession ARO:3003459
DefinitionPoint mutation in Mycobacterium tuberculosis gyrB resulting in fluoroquinolone resistance
AMR Gene Familyfluoroquinolone resistant gyrB
Drug Classfluoroquinolone antibiotic
Resistance Mechanismantibiotic target alteration
Classification12 ontology terms | Show
Parent Term(s)13 ontology terms | Show
+ fluoroquinolone resistant gyrB [AMR Gene Family]
+ confers_resistance_to_antibiotic enoxacin [Antibiotic]
+ confers_resistance_to_antibiotic gatifloxacin [Antibiotic]
+ confers_resistance_to_antibiotic grepafloxacin [Antibiotic]
+ confers_resistance_to_antibiotic levofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic lomefloxacin [Antibiotic]
+ confers_resistance_to_antibiotic moxifloxacin [Antibiotic]
+ confers_resistance_to_antibiotic nalidixic acid [Antibiotic]
+ confers_resistance_to_antibiotic norfloxacin [Antibiotic]
+ confers_resistance_to_antibiotic ofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic pefloxacin [Antibiotic]
+ confers_resistance_to_antibiotic sparfloxacin [Antibiotic]
+ confers_resistance_to_antibiotic trovafloxacin [Antibiotic]
Publications

Malik S, et al. 2012. PLoS ONE 7(6):e39754 New insights into fluoroquinolone resistance in Mycobacterium tuberculosis: functional genetic analysis of gyrA and gyrB mutations. (PMID 22761889)

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)

Resistomes

Prevalence of Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolone among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI for 82 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, 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).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGS
Mycobacterium tuberculosis1.3%0%1.9%
Show Perfect Only


Detection Models

Model Type: protein variant model

Model Definition: The protein variant model is an AMR detection model. Protein variant models are similar to protein homolog models - they detect the presence of a protein sequence based on its similarity to a curated reference sequence, but secondarily search submitted query sequences for curated sets of mutations shown clinically to confer resistance relative to wild-type. This model includes a protein reference sequence, a curated BLASTP cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of: single resistance variants, insertions, deletions, co-dependent resistance variants, nonsense SNPs, and/or frameshift mutations. Protein variant model matches to reference sequences are categorized on two criteria: strict and loose. A strict match has a BLASTP bitscore above the curated BLASTP cutoff value and contains at least one detected mutation from amongst the mapped resistance variants; a loose match has a BLASTP bitscore below the curated BLASTP cutoff value but still contains at least one detected mutation from amongst the mapped resistance variants. Regardless of BLASTP bitscore, if a sequence does not contain one of the mapped resistance variants, it is not considered a match and not detected by the protein variant model.

Legend:

  • discovered in clinical, agricultural, or environmental isolates
  • discovered via laboratory selection experiments


Bit-score Cut-off (blastP): 1200

PMID in progress (multiple): R485C,T546M

PMID: 22761889V340L R485C,T539N D500H N538D N538K N538D,T546M N538T,T546M T539N T539P E540D E540V 39879,G247S+40052,D500N
PMID: 16377674N510D 39879,A90V+40052,D472H

>gb|CAA55486.1|+|Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolone [Mycobacterium tuberculosis H37Ra]
MGKNEARRSALAPDHGTVVCDPLRRLNRMHATPEESIRIVAAQKKKAQDEYGAASITILE
GLEAVRKRPGMYIGSTGERGLHHLIWEVVDNAVDEAMAGYATTVNVVLLEDGGVEVADDG
RGIPVATHASGIPTVDVVMTQLHAGGKFDSDAYAISGGLHGVGVSVVNALSTRLEVEIKR
DGYEWSQVYEKSEPLGLKQGAPTKKTGSTVRFWADPAVFETTEYDFETVARRLQEMAFLN
KGLTINLTDERVTQDEVVDEVVSDVAEAPKSASERAAESTAPHKVKSRTFHYPGGLVDFV
KHINRTKNAIHSSIVDFSGKGTGHEVEIAMQWNAGYSESVHTFANTINTHEGGTHEEGFR
SALTSVVNKYAKDRKLLKDKDPNLTGDDIREGLAAVISVKVSEPQFEGQTKTKLGNTEVK
SFVQKVCNEQLTHWFEANPTDAKVVVNKAVSSAQARIAARKARELVRRKSATDIGGLPGK
LADCRSTDPRKSELYVVEGDSAGGSAKSGRDSMFQAILPLRGKIINVEKARIDRVLKNTE
VQAIITALGTGIHDEFDIGKLRYHKIVLMADADVDGQHISTLLLTLLFRFMRPLIENGHV
FLAQPPLYKLKWQRSDPEFAYSDRERDGLLEAGLKAGKKINKEDGIQRYKGLGEMDAKEL
WETTMDPSVRVLRQVTLDDAAAADELFSILMGEDVDARRSFITRNAKDVRFLDV



>gb|X78888.1|+|301-2445|Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolone [Mycobacterium tuberculosis H37Ra]
ATGGGTAAAAACGAGGCCAGAAGATCGGCCCTGGCGCCCGATCACGGTACAGTGGTGTGCGACCCCCTGCGGCGACTCAACCGCATGCAC
GCAACCCCTGAGGAGAGTATTCGGATCGTGGCTGCCCAGAAAAAGAAGGCCCAAGACGAATACGGCGCTGCGTCTATCACCATTCTCGAA
GGGCTGGAGGCCGTCCGCAAACGTCCCGGCATGTACATTGGCTCGACCGGTGAGCGCGGTTTACACCATCTCATTTGGGAGGTGGTCGAC
AACGCGGTCGACGAGGCGATGGCCGGTTATGCAACCACAGTGAACGTAGTGCTGCTTGAGGATGGCGGTGTCGAGGTCGCCGACGACGGC
CGCGGCATTCCGGTCGCCACCCACGCCTCCGGCATACCGACCGTCGACGTGGTGATGACACAACTACATGCCGGCGGCAAGTTCGACTCG
GACGCGTATGCGATATCTGGTGGTCTGCACGGCGTCGGCGTGTCGGTGGTTAACGCGCTATCCACCCGGCTCGAAGTCGAGATCAAGCGC
GACGGGTACGAGTGGTCTCAGGTTTATGAGAAGTCGGAACCCCTGGGCCTCAAGCAAGGGGCGCCGACCAAGAAGACGGGGTCAACGGTG
CGGTTCTGGGCCGACCCCGCTGTTTTCGAAACCACGGAATACGACTTCGAAACCGTCGCCCGCCGGCTGCAAGAGATGGCGTTCCTCAAC
AAGGGGCTGACCATCAACCTGACCGACGAGAGGGTGACCCAAGACGAGGTCGTCGACGAAGTGGTCAGCGACGTCGCCGAGGCGCCGAAG
TCGGCAAGTGAACGCGCAGCCGAATCCACTGCACCGCACAAAGTTAAGAGCCGCACCTTTCACTATCCGGGTGGCCTGGTGGACTTCGTG
AAACACATCAACCGCACCAAGAACGCGATTCATAGCAGCATCGTGGATTTTTCCGGCAAGGGCACCGGGCACGAGGTGGAGATCGCGATG
CAATGGAACGCCGGGTATTCGGAGTCGGTGCACACCTTCGCCAACACCATCAACACCCACGAGGGCGGCACCCACGAAGAGGGCTTCCGC
AGCGCGCTGACGTCGGTGGTGAACAAGTACGCCAAGGACCGCAAGCTACTGAAGGACAAGGACCCCAACCTCACCGGTGACGATATCCGG
GAAGGCCTGGCCGCTGTGATCTCGGTGAAGGTCAGCGAACCGCAGTTCGAGGGCCAGACCAAGACCAAGTTGGGCAACACCGAGGTCAAA
TCGTTTGTGCAGAAGGTCTGTAACGAACAGCTGACCCACTGGTTTGAAGCCAACCCCACCGACGCGAAAGTCGTTGTGAACAAGGCTGTG
TCCTCGGCGCAAGCCCGTATCGCGGCACGTAAGGCACGAGAGTTGGTGCGGCGTAAGAGCGCCACCGACATCGGTGGATTGCCCGGCAAG
CTGGCCGATTGCCGTTCCACGGATCCGCGCAAGTCCGAACTGTATGTCGTAGAAGGTGACTCGGCCGGCGGTTCTGCAAAAAGCGGTCGC
GATTCGATGTTCCAGGCGATACTTCCGCTGCGCGGCAAGATCATCAATGTGGAGAAAGCGCGCATCGACCGGGTGCTAAAGAACACCGAA
GTTCAGGCGATCATCACGGCGCTGGGCACCGGGATCCACGACGAGTTCGATATCGGCAAGCTGCGCTACCACAAGATCGTGCTGATGGCC
GACGCCGATGTTGACGGCCAACATATTTCCACGCTGTTGTTGACGTTGTTGTTCCGGTTCATGCGGCCGCTCATCGAGAACGGGCATGTG
TTTTTGGCACAACCGCCGCTGTACAAACTCAAGTGGCAGCGCAGTGACCCGGAATTCGCATACTCCGACCGCGAGCGCGACGGTCTGCTG
GAGGCGGGGCTGAAGGCCGGGAAGAAGATCAACAAGGAAGACGGCATTCAGCGGTACAAGGGTCTAGGTGAAATGGACGCTAAGGAGTTG
TGGGAGACCACCATGGATCCCTCGGTTCGTGTGTTGCGTCAAGTGACGCTGGACGACGCCGCCGCCGCCGACGAGTTGTTCTCCATCCTG
ATGGGCGAGGACGTCGACGCGCGGCGCAGCTTTATCACCCGCAACGCCAAGGATGTTCGGTTCCTGGATGTCTAA