Mycobacterium tuberculosis ndh with mutation conferring resistance to isoniazid

Accession ARO:3003461
CARD Short NameMtub_ndh_INH
DefinitionPoint mutations in the Mycobacterium tuberculosis ndh gene shown clinically to confer resistance to isoniazid.
AMR Gene Familyantibiotic resistant ndh
Drug Classisoniazid-like antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification8 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ antibiotic resistant ndh [AMR Gene Family]
+ confers_resistance_to_antibiotic isoniazid [Antibiotic]
Publications

Cardoso RF, et al. 2007. Mem Inst Oswaldo Cruz 102(1): 59-61. Characterization of ndh gene of isoniazid resistant and susceptible Mycobacterium tuberculosis isolates from Brazil. (PMID 17294000)

Jagielski T, et al. 2014. J. Antimicrob. Chemother. 69(9):2369-75 Detection of mutations associated with isoniazid resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates. (PMID 24855126)

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)

Rueda J, et al. 2015. Antimicrob. Agents Chemother. 59(12):7805-10 Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates. (PMID 26369965)

Jagielski T, et al. 2015. J. Antimicrob. Chemother. 70(12):3214-21 Mutation profiling for detection of isoniazid resistance in Mycobacterium tuberculosis clinical isolates. (PMID 26311839)

Islam MM, et al. 2019. Clin. Microbiol. Infect. 25(8):1041.e1-1041.e7 Detection of novel mutations associated with independent resistance and cross-resistance to isoniazid and prothionamide in Mycobacterium tuberculosis clinical isolates. (PMID 30583053)

Resistomes

Prevalence of Mycobacterium tuberculosis ndh with mutation 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 (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Mycobacterium tuberculosis6.35%0%2.06%0%
Show Perfect Only


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): 800

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID in progress (TB): -nt-132:G -nt-134:G

PMID: 17294000R13C V18A
PMID: 24855126V18A A300P
PMID: 26104204T110A R268H
PMID: 26369965G313R
PMID: 26311839V18A L50V A300P
PMID: 30583053G339A nt969+1:G

ReSeqTB:

High Confidence-nt-134:G
Minimal ConfidenceR268H
Indeterminate ConfidenceG313R -nt-132:G -nt-134:G

>gb|CCP44620.1|-|Mycobacterium tuberculosis ndh with mutation conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
MSPQQEPTAQPPRRHRVVIIGSGFGGLNAAKKLKRADVDIKLIARTTHHLFQPLLYQVAT
GIISEGEIAPPTRVVLRKQRNVQVLLGNVTHIDLAGQCVVSELLGHTYQTPYDSLIVAAG
AGQSYFGNDHFAEFAPGMKSIDDALELRGRILSAFEQAERSSDPERRAKLLTFTVVGAGP
TGVEMAGQIAELAEHTLKGAFRHIDSTKARVILLDAAPAVLPPMGAKLGQRAAARLQKLG
VEIQLGAMVTDVDRNGITVKDSDGTVRRIESACKVWSAGVSASRLGRDLAEQSRVELDRA
GRVQVLPDLSIPGYPNVFVVGDMAAVEGVPGVAQGAIQGAKYVASTIKAELAGANPAERE
PFQYFDKGSMATVSRFSAVAKIGPVEFSGFIAWLIWLVLHLAYLIGFKTKITTLLSWTVT
FLSTRRGQLTITDQQAFARTRLEQLAELAAEAQGSAASAKVAS



>gb|AL123456.3|-|2101651-2103042|Mycobacterium tuberculosis ndh with mutation conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
ATGAGTCCCCAGCAAGAACCCACAGCGCAACCACCTCGTAGGCATCGAGTTGTGATCATCGGATCTGGGTTCGGCGGGCTAAACGCGGCA
AAGAAGCTCAAGCGGGCCGACGTTGACATCAAGCTGATCGCGCGCACCACCCATCACCTGTTCCAGCCGCTGCTGTACCAAGTGGCCACC
GGGATTATCTCCGAGGGAGAAATCGCTCCGCCGACCCGGGTCGTGCTGCGTAAGCAGCGCAATGTCCAGGTACTGTTGGGCAACGTCACC
CACATCGACCTGGCCGGGCAGTGCGTCGTCTCGGAATTGCTCGGTCACACCTACCAAACCCCCTACGACAGCCTGATCGTCGCCGCGGGT
GCTGGCCAGTCTTATTTCGGCAACGACCATTTCGCCGAATTCGCACCCGGCATGAAGTCCATCGACGACGCGTTGGAGTTGCGTGGCCGC
ATATTGAGCGCTTTCGAGCAAGCCGAACGGTCCAGCGATCCGGAACGGCGGGCCAAGCTACTGACATTCACCGTTGTCGGGGCTGGCCCC
ACCGGTGTTGAAATGGCCGGACAGATCGCCGAGCTGGCCGAGCACACGTTGAAGGGCGCATTCCGGCACATCGACTCGACCAAGGCGCGG
GTGATTCTGCTTGACGCCGCCCCGGCGGTGCTGCCACCGATGGGCGCAAAGCTCGGTCAGCGGGCGGCTGCCCGGTTGCAGAAGCTGGGC
GTGGAAATCCAGCTGGGTGCGATGGTCACCGACGTCGACCGCAACGGCATCACCGTCAAGGACTCCGACGGCACCGTCCGGCGCATCGAG
TCGGCCTGCAAGGTCTGGTCGGCCGGGGTTTCGGCCAGTCGGTTGGGCAGGGACCTTGCCGAGCAATCACGGGTTGAGCTCGACCGGGCC
GGCCGGGTCCAAGTGCTGCCCGACCTGTCCATTCCCGGGTACCCGAACGTGTTCGTGGTGGGCGATATGGCCGCTGTGGAGGGTGTGCCG
GGTGTGGCGCAGGGCGCCATCCAGGGGGCGAAATACGTCGCCAGCACGATCAAGGCCGAACTGGCCGGCGCCAACCCGGCGGAGCGTGAG
CCATTCCAGTACTTCGACAAGGGATCGATGGCCACGGTTTCGAGGTTTTCGGCGGTGGCCAAGATCGGTCCCGTTGAGTTCAGCGGCTTT
ATCGCCTGGCTGATTTGGCTGGTGCTGCACCTGGCGTACCTGATCGGGTTCAAGACCAAGATCACCACTCTGCTGTCGTGGACGGTGACT
TTCCTCAGTACTCGCCGCGGCCAGCTGACCATCACCGACCAGCAGGCATTTGCGCGAACGCGGCTCGAACAGCTGGCCGAGCTGGCCGCC
GAGGCGCAGGGCTCAGCGGCAAGCGCTAAGGTGGCCAGCTAG