Mycobacterium tuberculosis ahpC mutations confer resistance to isoniazid

Download Sequences
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)

The CRyPTIC Consortium 2022. PLoS Biol 20(8):e3001721 A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics. (PMID 35944069)
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 414 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 GIGRDI-AMR2
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

PubMed: mutation data hand curated from the scientific literature, evaluated as conferring resistance (R). CRyPTIC: mutation data acquired from the CRyPTIC catalog, evaluated as resistant (R), susceptible (S), or undetermined (U). ReSeqTB: mutation data acquired from the ReSeqTB catalog, evaluated as conferring resistance (Minimal, Moderate, High), not conferring resistance (None), or Indeterminate. WHO: mutation data acquired from the WHO 2023 catalog, evaluated as resistant (R), susceptible (S), or undetermined (U).

MutationMutation typePubMedReSeqTBCRyPTICWHO
+nt47:tinsertion mutation from nucleotide sequenceno dataReSeqTB-Highno datano data
g-48asnp in promoter regionno datano dataCRyPTIC-Rno data
G48Asingle resistance variantno dataReSeqTB-Highno datano data
C52Tsingle resistance variantno dataReSeqTB-Highno datano data
c-57tsnp in promoter regionno datano dataCRyPTIC-Rno data
c-72tsnp in promoter regionno datano dataCRyPTIC-Rno data
C72Tsingle resistance variantno dataReSeqTB-Highno datano data
C81Tsingle resistance variantno dataReSeqTB-Highno datano data

>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

Curator Acknowledgements
Curator Description Most Recent Edit