Mycobacterium tuberculosis fabG1 mutations confer resistance to isoniazid

Download Sequences
Accession ARO:3004922
Synonym(s)Rv1483
CARD Short NameMtub_fabG1_INH
DefinitionMutations that occur in fabG1 resulting in or contributing to resistance in isoniazid.
AMR Gene Familyisoniazid resistant fabG1
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 fabG1 [AMR Gene Family]
Publications

Lavender C, et al. 2005. Antimicrob Agents Chemother 49(10):4068-74 Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis isolates collected in Australia. (PMID 16189082)

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)

World Health Organization. 2023. ISBN 978-92-4-008241-0. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Second Edition. (ISBN 978-92-4-008241-0)
Resistomes

Prevalence of Mycobacterium tuberculosis fabG1 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): 425

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
t-8asnp in promoter regionno datano datano dataWHO-R
t-8gsnp in promoter regionno datano datano dataWHO-R
t-8Varsnp in promoter regionno datano dataCRyPTIC-Rno data
t-8csnp in promoter regionno datano dataCRyPTIC-RWHO-R
c-15tsnp in promoter regionno datano dataCRyPTIC-RWHO-R
c-15Varsnp in promoter regionno datano dataCRyPTIC-Rno data
a-16Varsnp in promoter regionno datano dataCRyPTIC-Rno data
a-16gsnp in promoter regionno datano datano dataWHO-R
g-17tsnp in promoter regionno datano dataCRyPTIC-RWHO-R
L203Lsingle resistance variantno datano dataCRyPTIC-Rno data

>gb|NP_215999.1|+|Mycobacterium tuberculosis fabG1 mutations confer resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
MTATATEGAKPPFVSRSVLVTGGNRGIGLAIAQRLAADGHKVAVTHRGSGAPKGLFGVEC
DVTDSDAVDRAFTAVEEHQGPVEVLVSNAGLSADAFLMRMTEEKFEKVINANLTGAFRVA
QRASRSMQRNKFGRMIFIGSVSGSWGIGNQANYAASKAGVIGMARSIARELSKANVTANV
VAPGYIDTDMTRALDERIQQGALQFIPAKRVGTPAEVAGVVSFLASEDASYISGAVIPVD
GGMGMGH


>gb|NC_000962.3|+|1673440-1674183|Mycobacterium tuberculosis fabG1 mutations confer resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
GTGACTGCCACAGCCACTGAAGGGGCCAAACCCCCATTCGTATCCCGTTCAGTCCTGGTTACCGGAGGAAACCGGGGGATCGGGCTGGCG
ATCGCACAGCGGCTGGCTGCCGACGGCCACAAGGTGGCCGTCACCCACCGTGGATCCGGAGCGCCAAAGGGGCTGTTTGGCGTCGAATGT
GACGTCACCGACAGCGACGCCGTCGATCGCGCCTTCACGGCGGTAGAAGAGCACCAGGGTCCGGTCGAGGTGCTGGTGTCCAACGCCGGC
CTATCCGCGGACGCATTCCTCATGCGGATGACCGAGGAAAAGTTCGAGAAGGTCATCAACGCCAACCTCACCGGGGCGTTCCGGGTGGCT
CAACGGGCATCGCGCAGCATGCAGCGCAACAAATTCGGTCGAATGATATTCATAGGTTCGGTCTCCGGCAGCTGGGGCATCGGCAACCAG
GCCAACTACGCAGCCTCCAAGGCCGGAGTGATTGGCATGGCCCGCTCGATCGCCCGCGAGCTGTCGAAGGCAAACGTGACCGCGAATGTG
GTGGCCCCGGGCTACATCGACACCGATATGACCCGCGCGCTGGATGAGCGGATTCAGCAGGGGGCGCTGCAATTTATCCCAGCGAAGCGG
GTCGGCACCCCCGCCGAGGTCGCCGGGGTGGTCAGCTTCCTGGCTTCCGAGGATGCGAGCTATATCTCCGGTGCGGTCATCCCGGTCGAC
GGCGGCATGGGTATGGGCCACTGA

Curator Acknowledgements
Curator Description Most Recent Edit