Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolones

Accession ARO:3003459
Synonym(s)Rv0005
CARD Short NameMtub_gyrB_FLO
DefinitionPoint mutation in Mycobacterium tuberculosis gyrB resulting in fluoroquinolone resistance.
AMR Gene Familyfluoroquinolone resistant gyrB
Drug Classfluoroquinolone antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium aviumg, Mycobacterium tuberculosisg+wgs
Classification11 ontology terms | Show
Parent Term(s)13 ontology terms | Show
+ confers_resistance_to_antibiotic enoxacin [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 gyrB [AMR Gene Family]
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)

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)

Resistomes

Prevalence of Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolones among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 413 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).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Mycobacterium avium2.44%0%0%0%
Mycobacterium tuberculosis0.61%0%1.4%0%
Show Perfect Only


Detection Models

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): 1200

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 22761889V340L R485C,T539N R485C,T546M D500H N538D N538K N538D,T546M N538T,T546M T539N T539P E540D E540V 39879,G247S+40052,D500N
PMID: 16377674N510D 39879,A90V+40052,D472H
PMID: 30337678P94L I271M M291I V457L N499T E501D

ReSeqTB:

High ConfidenceE501D N499T
Moderate ConfidenceV457L
Indeterminate ConfidenceI271M

>gb|NP_214519.2|+|Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolones [Mycobacterium tuberculosis H37Rv]
MAAQKKKAQDEYGAASITILEGLEAVRKRPGMYIGSTGERGLHHLIWEVVDNAVDEAMAG
YATTVNVVLLEDGGVEVADDGRGIPVATHASGIPTVDVVMTQLHAGGKFDSDAYAISGGL
HGVGVSVVNALSTRLEVEIKRDGYEWSQVYEKSEPLGLKQGAPTKKTGSTVRFWADPAVF
ETTEYDFETVARRLQEMAFLNKGLTINLTDERVTQDEVVDEVVSDVAEAPKSASERAAES
TAPHKVKSRTFHYPGGLVDFVKHINRTKNAIHSSIVDFSGKGTGHEVEIAMQWNAGYSES
VHTFANTINTHEGGTHEEGFRSALTSVVNKYAKDRKLLKDKDPNLTGDDIREGLAAVISV
KVSEPQFEGQTKTKLGNTEVKSFVQKVCNEQLTHWFEANPTDAKVVVNKAVSSAQARIAA
RKARELVRRKSATDIGGLPGKLADCRSTDPRKSELYVVEGDSAGGSAKSGRDSMFQAILP
LRGKIINVEKARIDRVLKNTEVQAIITALGTGIHDEFDIGKLRYHKIVLMADADVDGQHI
STLLLTLLFRFMRPLIENGHVFLAQPPLYKLKWQRSDPEFAYSDRERDGLLEAGLKAGKK
INKEDGIQRYKGLGEMDAKELWETTMDPSVRVLRQVTLDDAAAADELFSILMGEDVDARR
SFITRNAKDVRFLDV



>gb|NC_000962.3|+|5240-7267|Mycobacterium tuberculosis gyrB mutant conferring resistance to fluoroquinolones [Mycobacterium tuberculosis H37Rv]
GTGGCTGCCCAGAAAAAGAAGGCCCAAGACGAATACGGCGCTGCGTCTATCACCATTCTCGAAGGGCTGGAGGCCGTCCGCAAACGTCCC
GGCATGTACATTGGCTCGACCGGTGAGCGCGGTTTACACCATCTCATTTGGGAGGTGGTCGACAACGCGGTCGACGAGGCGATGGCCGGT
TATGCAACCACAGTGAACGTAGTGCTGCTTGAGGATGGCGGTGTCGAGGTCGCCGACGACGGCCGCGGCATTCCGGTCGCCACCCACGCC
TCCGGCATACCGACCGTCGACGTGGTGATGACACAACTACATGCCGGCGGCAAGTTCGACTCGGACGCGTATGCGATATCTGGTGGTCTG
CACGGCGTCGGCGTGTCGGTGGTTAACGCGCTATCCACCCGGCTCGAAGTCGAGATCAAGCGCGACGGGTACGAGTGGTCTCAGGTTTAT
GAGAAGTCGGAACCCCTGGGCCTCAAGCAAGGGGCGCCGACCAAGAAGACGGGGTCAACGGTGCGGTTCTGGGCCGACCCCGCTGTTTTC
GAAACCACGGAATACGACTTCGAAACCGTCGCCCGCCGGCTGCAAGAGATGGCGTTCCTCAACAAGGGGCTGACCATCAACCTGACCGAC
GAGAGGGTGACCCAAGACGAGGTCGTCGACGAAGTGGTCAGCGACGTCGCCGAGGCGCCGAAGTCGGCAAGTGAACGCGCAGCCGAATCC
ACTGCACCGCACAAAGTTAAGAGCCGCACCTTTCACTATCCGGGTGGCCTGGTGGACTTCGTGAAACACATCAACCGCACCAAGAACGCG
ATTCATAGCAGCATCGTGGACTTTTCCGGCAAGGGCACCGGGCACGAGGTGGAGATCGCGATGCAATGGAACGCCGGGTATTCGGAGTCG
GTGCACACCTTCGCCAACACCATCAACACCCACGAGGGCGGCACCCACGAAGAGGGCTTCCGCAGCGCGCTGACGTCGGTGGTGAACAAG
TACGCCAAGGACCGCAAGCTACTGAAGGACAAGGACCCCAACCTCACCGGTGACGATATCCGGGAAGGCCTGGCCGCTGTGATCTCGGTG
AAGGTCAGCGAACCGCAGTTCGAGGGCCAGACCAAGACCAAGTTGGGCAACACCGAGGTCAAATCGTTTGTGCAGAAGGTCTGTAACGAA
CAGCTGACCCACTGGTTTGAAGCCAACCCCACCGACGCGAAAGTCGTTGTGAACAAGGCTGTGTCCTCGGCGCAAGCCCGTATCGCGGCA
CGTAAGGCACGAGAGTTGGTGCGGCGTAAGAGCGCCACCGACATCGGTGGATTGCCCGGCAAGCTGGCCGATTGCCGTTCCACGGATCCG
CGCAAGTCCGAACTGTATGTCGTAGAAGGTGACTCGGCCGGCGGTTCTGCAAAAAGCGGTCGCGATTCGATGTTCCAGGCGATACTTCCG
CTGCGCGGCAAGATCATCAATGTGGAGAAAGCGCGCATCGACCGGGTGCTAAAGAACACCGAAGTTCAGGCGATCATCACGGCGCTGGGC
ACCGGGATCCACGACGAGTTCGATATCGGCAAGCTGCGCTACCACAAGATCGTGCTGATGGCCGACGCCGATGTTGACGGCCAACATATT
TCCACGCTGTTGTTGACGTTGTTGTTCCGGTTCATGCGGCCGCTCATCGAGAACGGGCATGTGTTTTTGGCACAACCGCCGCTGTACAAA
CTCAAGTGGCAGCGCAGTGACCCGGAATTCGCATACTCCGACCGCGAGCGCGACGGTCTGCTGGAGGCGGGGCTGAAGGCCGGGAAGAAG
ATCAACAAGGAAGACGGCATTCAGCGGTACAAGGGTCTAGGTGAAATGGACGCTAAGGAGTTGTGGGAGACCACCATGGATCCCTCGGTT
CGTGTGTTGCGTCAAGTGACGCTGGACGACGCCGCCGCCGCCGACGAGTTGTTCTCCATCCTGATGGGCGAGGACGTCGACGCGCGGCGC
AGCTTTATCACCCGCAACGCCAAGGATGTTCGGTTCCTGGATGTCTAA