Mycobacterium tuberculosis furA mutations confer resistance to isoniazid

Accession ARO:3004923
Synonym(s)Rv1909c
CARD Short NameMtub_furA_INH
DefinitionMutations that occur in furA that result in or contribute to antibiotic resistance to isoniazid.
AMR Gene Familyisoniazid resistant furA
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 furA [AMR Gene Family]
Publications

Siu GK, et al. 2014. Antimicrob Agents Chemother 58(10):6093-100 An upstream truncation of the furA-katG operon confers high-level isoniazid resistance in a Mycobacterium tuberculosis clinical isolate with no known resistance-associated mutations. (PMID 25092698)

Nebenzahl-Guimaraes H, et al. 2014. J Antimicrob Chemother 69(2):331-42 Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis. (PMID 24055765)

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 furA 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): 225

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
A14Vsingle resistance variantno dataReSeqTB-Moderateno datano data

>gb|NP_216425.2|-|Mycobacterium tuberculosis furA mutations confer resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
MSSIPDYAEQLRTADLRVTRPRVAVLEAVNAHPHADTETIFGAVRFALPDVSRQAVYDVL
HALTAAGLVRKIQPSGSVARYESRVGDNHHHIVCRSCGVIADVDCAVGEAPCLTASDHNG
FLLDEAEVIYWGLCPDCSISDTSRSHP



>gb|NC_000962.3|-|2156149-2156592|Mycobacterium tuberculosis furA mutations confer resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
GTGTCCTCTATACCGGACTACGCCGAACAGCTCCGGACGGCCGACCTGCGCGTGACCCGACCGCGCGTCGCCGTCCTGGAAGCAGTGAAT
GCGCATCCACACGCCGACACGGAAACGATTTTCGGTGCCGTGCGTTTTGCGCTGCCCGACGTATCCCGGCAAGCCGTGTACGACGTGCTG
CATGCCCTGACCGCCGCGGGCTTGGTGCGAAAGATCCAACCCTCGGGCTCCGTCGCGCGCTACGAGTCCAGGGTCGGCGACAACCACCAT
CACATCGTCTGCCGGTCTTGCGGGGTTATCGCCGATGTCGACTGTGCTGTTGGCGAGGCACCCTGTCTGACGGCCTCGGACCATAACGGC
TTCCTGTTGGACGAGGCGGAGGTCATCTACTGGGGTCTATGTCCTGATTGTTCGATATCCGACACTTCGCGATCACATCCGTGA

Curator Acknowledgements
Curator Description Most Recent Edit