Mycobacterium tuberculosis kasA mutant conferring resistance to isoniazid

Accession ARO:3003463
CARD Short NameMtub_kasA_INH
DefinitionSpecific mutations on the Mycobacterium tuberculosis kasA gene resulting in lowered affinity of isoniazid, resulting in resistance.
AMR Gene Familyantibiotic resistant kasA
Drug Classisoniazid-like antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification8 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ antibiotic resistant kasA [AMR Gene Family]
+ confers_resistance_to_antibiotic isoniazid [Antibiotic]
Publications

Lee AS, et al. 1999. Antimicrob Agents Chemother 43(8): 2087-2089. Contribution of kasA analysis to detection of isoniazid-resistant Mycobacterium tuberculosis in Singapore. (PMID 10428945)

Mdluli K, et al. 1998. Science 280(5369): 1607-1610. Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid. (PMID 9616124)

Resistomes

Prevalence of Mycobacterium tuberculosis kasA mutant conferring resistance to isoniazid 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 tuberculosis8.61%0%15.85%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): 750

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 10428945R121K G269S G312S G387D
PMID: 9616124D66N F413L

>gb|CCP45025.1|+|Mycobacterium tuberculosis kasA mutant conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
MSQPSTANGGFPSVVVTAVTATTSISPDIESTWKGLLAGESGIHALEDEFVTKWDLAVKI
GGHLKDPVDSHMGRLDMRRMSYVQRMGKLLGGQLWESAGSPEVDPDRFAVVVGTGLGGAE
RIVESYDLMNAGGPRKVSPLAVQMIMPNGAAAVIGLQLGARAGVMTPVSACSSGSEAIAH
AWRQIVMGDADVAVCGGVEGPIEALPIAAFSMMRAMSTRNDEPERASRPFDKDRDGFVFG
EAGALMLIETEEHAKARGAKPLARLLGAGITSDAFHMVAPAADGVRAGRAMTRSLELAGL
SPADIDHVNAHGTATPIGDAAEANAIRVAGCDQAAVYAPKSALGHSIGAVGALESVLTVL
TLRDGVIPPTLNYETPDPEIDLDVVAGEPRYGDYRYAVNNSFGFGGHNVALAFGRY



>gb|AL123456.1|+|2518115-2519365|Mycobacterium tuberculosis kasA mutant conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
GTGAGTCAGCCTTCCACCGCTAATGGCGGTTTCCCCAGCGTTGTGGTGACCGCCGTCACAGCGACGACGTCGATCTCGCCGGACATCGAG
AGCACGTGGAAGGGTCTGTTGGCCGGCGAGAGCGGCATCCACGCACTCGAAGACGAGTTCGTCACCAAGTGGGATCTAGCGGTCAAGATC
GGCGGTCACCTCAAGGATCCGGTCGACAGCCACATGGGCCGACTCGACATGCGACGCATGTCGTACGTCCAGCGGATGGGCAAGTTGCTG
GGCGGACAGCTATGGGAGTCCGCCGGCAGCCCGGAGGTCGATCCAGACCGGTTCGCCGTTGTTGTCGGCACCGGTCTAGGTGGAGCCGAG
AGGATTGTCGAGAGCTACGACCTGATGAATGCGGGCGGCCCCCGGAAGGTGTCCCCGCTGGCCGTTCAGATGATCATGCCCAACGGTGCC
GCGGCGGTGATCGGTCTGCAGCTTGGGGCCCGCGCCGGGGTGATGACCCCGGTGTCGGCCTGTTCGTCGGGCTCGGAAGCGATCGCCCAC
GCGTGGCGTCAGATCGTGATGGGCGACGCCGACGTCGCCGTCTGCGGCGGTGTCGAAGGACCCATCGAGGCGCTGCCCATCGCGGCGTTC
TCCATGATGCGGGCCATGTCGACCCGCAACGACGAGCCTGAGCGGGCCTCCCGGCCGTTCGACAAGGACCGCGACGGCTTTGTGTTCGGC
GAGGCCGGTGCGCTGATGCTCATCGAGACGGAGGAGCACGCCAAAGCCCGTGGCGCCAAGCCGTTGGCCCGATTGCTGGGTGCCGGTATC
ACCTCGGACGCCTTTCATATGGTGGCGCCCGCGGCCGATGGTGTTCGTGCCGGTAGGGCGATGACTCGCTCGCTGGAGCTGGCCGGGTTG
TCGCCGGCGGACATCGACCACGTCAACGCGCACGGCACGGCGACGCCTATCGGCGACGCCGCGGAGGCCAACGCCATCCGCGTCGCCGGT
TGTGATCAGGCCGCGGTGTACGCGCCGAAGTCTGCGCTGGGCCACTCGATCGGCGCGGTCGGTGCGCTCGAGTCGGTGCTCACGGTGCTG
ACGCTGCGCGACGGCGTCATCCCGCCGACCCTGAACTACGAGACACCCGATCCCGAGATCGACCTTGACGTCGTCGCCGGCGAACCGCGC
TATGGCGATTACCGCTACGCAGTCAACAACTCGTTCGGGTTCGGCGGCCACAATGTGGCGCTTGCCTTCGGGCGTTACTGA