Mycobacterium tuberculosis nat mutations conferring resistance to isoniazid

Accession ARO:3004930
Synonym(s)Rv3566c
CARD Short NameMtub_nat_INH
DefinitionMutations that occur in nat which through overexpression of the enzyme can result in or contribute to antibiotic resistance to isoniazid.
AMR Gene Familyisoniazid resistant nat
Drug Classisoniazid-like antibiotic
Resistance Mechanismantibiotic target alteration
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic isoniazid [Antibiotic]
+ isoniazid resistant nat [AMR Gene Family]
Publications

Vilchèze C, et al. 2014. Microbiol Spectr 2(4):MGM2-0014-2013 Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities. (PMID 26104204)

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 nat mutations 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

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
No prevalence data


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): 500

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 30337678Y177H A196A G207R ntG-183A

ReSeqTB:

High ConfidenceA196A ntG-183A

>gb|YP_177989.1|-|Mycobacterium tuberculosis nat mutations conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
MALDLTAYFDRINYRGATDPTLDVLQDLVTVHSRTIPFENLDPLLGVPVDDLSPQALADK
LVLRRRGGYCFEHNGLMGYVLAELGYRVRRFAARVVWKLAPDAPLPPQTHTLLGVTFPGS
GGCYLVDVGFGGQTPTSPLRLETGAVQPTTHEPYRLEDRVDGFVLQAMVRDTWQTLYEFT
TQTRPQIDLKVASWYASTHPASKFVTGLTAAVITDDARWNLSGRDLAVHRAGGTEKIRLA
DAAAVVDTLSERFGINVADIGERGALETRIDELLARQPGADAP



>gb|NC_000962.3|-|4007331-4008182|Mycobacterium tuberculosis nat mutations conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
ATGGCACTGGATCTGACCGCGTACTTCGATCGCATCAACTATCGCGGCGCTACCGATCCAACCCTGGATGTTCTGCAGGATCTGGTGACC
GTGCACAGTCGAACGATTCCGTTCGAGAACCTCGACCCGCTGCTGGGGGTGCCGGTCGACGACCTCAGTCCACAGGCGCTGGCCGACAAG
CTGGTACTTCGGCGCCGAGGCGGGTACTGCTTTGAGCACAACGGGCTGATGGGTTATGTGCTGGCCGAACTCGGCTATCGGGTGCGCCGA
TTCGCCGCCCGCGTCGTCTGGAAGCTCGCGCCGGACGCGCCCCTGCCGCCGCAGACGCACACCCTGCTGGGGGTCACGTTCCCCGGCTCG
GGCGGATGCTATCTCGTCGACGTCGGATTCGGCGGCCAAACACCGACCTCACCGCTTCGCCTCGAAACCGGCGCCGTCCAGCCGACAACG
CACGAACCTTATCGGCTCGAGGACCGCGTCGACGGCTTTGTCTTGCAGGCGATGGTCCGGGACACATGGCAGACACTGTACGAATTCACC
ACCCAGACCCGCCCGCAGATCGATCTGAAAGTGGCCAGCTGGTACGCCTCAACACACCCGGCATCGAAGTTCGTCACGGGACTGACCGCC
GCGGTGATCACCGACGACGCCCGGTGGAACCTATCTGGCCGCGACCTTGCCGTTCACCGTGCCGGTGGTACCGAGAAGATCCGCCTTGCC
GATGCGGCAGCGGTTGTCGACACCCTGAGCGAACGGTTCGGGATCAACGTGGCAGATATCGGCGAGCGCGGCGCGCTCGAGACGCGCATC
GACGAGCTATTGGCTCGGCAGCCAGGAGCCGATGCGCCGTAA