Mycobacterium tuberculosis ahpC mutations confer resistance to isoniazid

Accession ARO:3004921
Synonym(s)Rv2428
CARD Short NameMtub_ahpC_INH
DefinitionMutations that occur in ahpC that result in ahpC overexpression thus conferring or contributing to resistance to isoniazid.
AMR Gene FamilyIsoniazid resistant ahpC
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 ahpC [AMR Gene Family]
Publications

Wilson TM, et al. 1996. Mol Microbiol 19(5):1025-34 ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex. (PMID 8830260)

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 ahpC mutations confer 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): 325

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 30337678P44R G48A C52T W53L C72T G74A C81T L191F +nt-47:T

ReSeqTB:

High Confidence+nt-47:T C52T C72T C81T G48A

>gb|NP_216944.1|+|Mycobacterium tuberculosis ahpC mutations confer resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
MPLLTIGDQFPAYQLTALIGGDLSKVDAKQPGDYFTTITSDEHPGKWRVVFFWPKDFTFV
CPTEIAAFSKLNDEFEDRDAQILGVSIDSEFAHFQWRAQHNDLKTLPFPMLSDIKRELSQ
AAGVLNADGVADRVTFIVDPNNEIQFVSATAGSVGRNVDEVLRVLDALQSDELCACNWRK
GDPTLDAGELLKASA



>gb|NC_000962.3|+|2726193-2726780|Mycobacterium tuberculosis ahpC mutations confer resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
ATGCCACTGCTAACCATTGGCGATCAATTCCCCGCCTACCAGCTCACCGCTCTCATCGGCGGTGACCTGTCCAAGGTCGACGCCAAGCAG
CCCGGCGACTACTTCACCACTATCACCAGTGACGAACACCCAGGCAAGTGGCGGGTGGTGTTCTTTTGGCCGAAAGACTTCACGTTCGTG
TGCCCTACCGAGATCGCGGCGTTCAGCAAGCTCAATGACGAGTTCGAGGACCGCGACGCCCAGATCCTGGGGGTTTCGATTGACAGCGAA
TTCGCGCATTTCCAGTGGCGTGCACAGCACAACGACCTCAAAACGTTACCCTTCCCGATGCTCTCCGACATCAAGCGCGAACTCAGCCAA
GCCGCAGGTGTCCTCAACGCCGACGGTGTGGCCGACCGCGTGACCTTTATCGTCGACCCCAACAACGAGATCCAGTTCGTCTCGGCCACC
GCCGGTTCGGTGGGACGCAACGTCGATGAGGTACTGCGAGTGCTCGACGCCCTCCAGTCCGACGAGCTGTGCGCATGCAACTGGCGCAAG
GGCGACCCGACGCTAGACGCTGGCGAACTCCTCAAGGCTTCGGCCTAA