Mycobacterium tuberculosis gyrA conferring resistance to fluoroquinolones

Accession ARO:3003295
DefinitionPoint mutation of Mycobacterium tuberculosis gyrA resulted in the lowered affinity between fluoroquinolones and gyrA. Thus, conferring resistance.
AMR Gene Familyfluoroquinolone resistant gyrA
Drug Classfluoroquinolone antibiotic
Resistance Mechanismantibiotic target alteration
Classification12 ontology terms | Show
Parent Term(s)14 ontology terms | Show
+ fluoroquinolone resistant gyrA [AMR Gene Family]
+ confers_resistance_to_antibiotic ciprofloxacin [Antibiotic]
+ 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

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)

Resistomes

Prevalence of Mycobacterium tuberculosis gyrA conferring resistance to fluoroquinolones 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 tuberculosis10.39%0%15.25%
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): 1500

PMID: 21300839G88C G88A D89G D89N D89V A90V A90G S91P D94A D94V D94Y D94G D94N 39879,G247S+40052,D500N
PMID: 17035499A74S T80A
PMID: 16377674T80A A90V,D94G 39879,A90V+40052,D472H
PMID: 16584301P102H
PMID: 27847014D94T

>gb|CCP42728.1|+|Mycobacterium tuberculosis gyrA conferring resistance to fluoroquinolones [Mycobacterium tuberculosis H37Rv]
MTDTTLPPDDSLDRIEPVDIEQEMQRSYIDYAMSVIVGRALPEVRDGLKPVHRRVLYAMF
DSGFRPDRSHAKSARSVAETMGNYHPHGDASIYDSLVRMAQPWSLRYPLVDGQGNFGSPG
NDPPAAMRYTEARLTPLAMEMLREIDEETVDFIPNYDGRVQEPTVLPSRFPNLLANGSGG
IAVGMATNIPPHNLRELADAVFWALENHDADEEETLAAVMGRVKGPDFPTAGLIVGSQGT
ADAYKTGRGSIRMRGVVEVEEDSRGRTSLVITELPYQVNHDNFITSIAEQVRDGKLAGIS
NIEDQSSDRVGLRIVIEIKRDAVAKVVINNLYKHTQLQTSFGANMLAIVDGVPRTLRLDQ
LIRYYVDHQLDVIVRRTTYRLRKANERAHILRGLVKALDALDEVIALIRASETVDIARAG
LIELLDIDEIQAQAILDMQLRRLAALERQRIIDDLAKIEAEIADLEDILAKPERQRGIVR
DELAEIVDRHGDDRRTRIIAADGDVSDEDLIAREDVVVTITETGYAKRTKTDLYRSQKRG
GKGVQGAGLKQDDIVAHFFVCSTHDLILFFTTQGRVYRAKAYDLPEASRTARGQHVANLL
AFQPEERIAQVIQIRGYTDAPYLVLATRNGLVKKSKLTDFDSNRSGGIVAVNLRDNDELV
GAVLCSAGDDLLLVSANGQSIRFSATDEALRPMGRATSGVQGMRFNIDDRLLSLNVVREG
TYLLVATSGGYAKRTAIEEYPVQGRGGKGVLTVMYDRRRGRLVGALIVDDDSELYAVTSG
GGVIRTAARQVRKAGRQTKGVRLMNLGEGDTLLAIARNAEESGDDNAVDANGADQTGN



>gb|AL123456|+|7302-9818|Mycobacterium tuberculosis gyrA conferring resistance to fluoroquinolones [Mycobacterium tuberculosis H37Rv]
ATGACAGACACGACGTTGCCGCCTGACGACTCGCTCGACCGGATCGAACCGGTTGACATCGAGCAGGAGATGCAGCGCAGCTACATCGAC
TATGCGATGAGCGTGATCGTCGGCCGCGCGCTGCCGGAGGTGCGCGACGGGCTCAAGCCCGTGCATCGCCGGGTGCTCTATGCAATGTTC
GATTCCGGCTTCCGCCCGGACCGCAGCCACGCCAAGTCGGCCCGGTCGGTTGCCGAGACCATGGGCAACTACCACCCGCACGGCGACGCG
TCGATCTACGACAGCCTGGTGCGCATGGCCCAGCCCTGGTCGCTGCGCTACCCGCTGGTGGACGGCCAGGGCAACTTCGGCTCGCCAGGC
AATGACCCACCGGCGGCGATGAGGTACACCGAAGCCCGGCTGACCCCGTTGGCGATGGAGATGCTGAGGGAAATCGACGAGGAGACAGTC
GATTTCATCCCTAACTACGACGGCCGGGTGCAAGAGCCGACGGTGCTACCCAGCCGGTTCCCCAACCTGCTGGCCAACGGGTCAGGCGGC
ATCGCGGTCGGCATGGCAACCAATATCCCGCCGCACAACCTGCGTGAGCTGGCCGACGCGGTGTTCTGGGCGCTGGAGAATCACGACGCC
GACGAAGAGGAGACCCTGGCCGCGGTCATGGGGCGGGTTAAAGGCCCGGACTTCCCGACCGCCGGACTGATCGTCGGATCCCAGGGCACC
GCTGATGCCTACAAAACTGGCCGCGGCTCCATTCGAATGCGCGGAGTTGTTGAGGTAGAAGAGGATTCCCGCGGTCGTACCTCGCTGGTG
ATCACCGAGTTGCCGTATCAGGTCAACCACGACAACTTCATCACTTCGATCGCCGAACAGGTCCGAGACGGCAAGCTGGCCGGCATTTCC
AACATTGAGGACCAGTCTAGCGATCGGGTCGGTTTACGCATCGTCATCGAGATCAAGCGCGATGCGGTGGCCAAGGTGGTGATCAATAAC
CTTTACAAGCACACCCAGCTGCAGACCAGCTTTGGCGCCAACATGCTAGCGATCGTCGACGGGGTGCCGCGCACGCTGCGGCTGGACCAG
CTGATCCGCTATTACGTTGACCACCAACTCGACGTCATTGTGCGGCGCACCACCTACCGGCTGCGCAAGGCAAACGAGCGAGCCCACATT
CTGCGCGGCCTGGTTAAAGCGCTCGACGCGCTGGACGAGGTCATTGCACTGATCCGGGCGTCGGAGACCGTCGATATCGCCCGGGCCGGA
CTGATCGAGCTGCTCGACATCGACGAGATCCAGGCCCAGGCAATCCTGGACATGCAGTTGCGGCGCCTGGCCGCACTGGAACGCCAGCGC
ATCATCGACGACCTGGCCAAAATCGAGGCCGAGATCGCCGATCTGGAAGACATCCTGGCAAAACCCGAGCGGCAGCGTGGGATCGTGCGC
GACGAACTCGCCGAAATCGTGGACAGGCACGGCGACGACCGGCGTACCCGGATCATCGCGGCCGACGGAGACGTCAGCGACGAGGATTTG
ATCGCCCGCGAGGACGTCGTTGTCACTATCACCGAAACGGGATACGCCAAGCGCACCAAGACCGATCTGTATCGCAGCCAGAAACGCGGC
GGCAAGGGCGTGCAGGGTGCGGGGTTGAAGCAGGACGACATCGTCGCGCACTTCTTCGTGTGCTCCACCCACGATTTGATCCTGTTCTTC
ACCACCCAGGGACGGGTTTATCGGGCCAAGGCCTACGACTTGCCCGAGGCCTCCCGGACGGCGCGCGGGCAGCACGTGGCCAACCTGTTA
GCCTTCCAGCCCGAGGAACGCATCGCCCAGGTCATCCAGATTCGCGGCTACACCGACGCCCCGTACCTGGTGCTGGCCACTCGCAACGGG
CTGGTGAAAAAGTCCAAGCTGACCGACTTCGACTCCAATCGCTCGGGCGGAATCGTGGCGGTCAACCTGCGCGACAACGACGAGCTGGTC
GGTGCGGTGCTGTGTTCGGCCGGCGACGACCTGCTGCTGGTCTCGGCCAACGGGCAGTCCATCAGGTTCTCGGCGACCGACGAGGCGCTG
CGGCCAATGGGTCGTGCCACCTCGGGTGTGCAGGGCATGCGGTTCAATATCGACGACCGGCTGCTGTCGCTGAACGTCGTGCGTGAAGGC
ACCTATCTGCTGGTGGCGACGTCAGGGGGCTATGCGAAACGTACCGCGATCGAGGAATACCCGGTACAGGGCCGCGGCGGTAAAGGTGTG
CTGACGGTCATGTACGACCGCCGGCGCGGCAGGTTGGTTGGGGCGTTGATTGTCGACGACGACAGCGAGCTGTATGCCGTCACTTCCGGC
GGTGGCGTGATCCGCACCGCGGCACGCCAGGTTCGCAAGGCGGGACGGCAGACCAAGGGTGTTCGGTTGATGAATCTGGGCGAGGGCGAC
ACACTGTTGGCCATCGCGCGCAACGCCGAAGAAAGTGGCGACGATAATGCCGTGGACGCCAACGGCGCAGACCAGACGGGCAATTAA