Mycobacterium tuberculosis ndh with mutation conferring resistance to isoniazid

Accession ARO:3003461
DefinitionPoint mutations in the Mycobacterium tuberculosis ndh gene shown clinically to confer resistance to isoniazid.
AMR Gene Familyantibiotic resistant ndh
Drug Classisoniazid
Resistance Mechanismantibiotic target alteration
Classification10 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic isoniazid [Drug Class]
+ antibiotic resistant ndh [AMR Gene Family]
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)

Vilch├Ęze 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)

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 for 82 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, 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 WGS
Mycobacterium tuberculosis11.69%0%3.23%
Show Perfect Only


Detection Models

Model Type: protein variant model

Model Definition: The protein variant model is an AMR detection model. Protein variant models are similar to protein homolog models - they detect the presence of a protein sequence based on its similarity to a curated reference sequence, but secondarily search submitted query sequences for curated sets of mutations shown clinically to confer resistance relative to wild-type. This model includes a protein reference sequence, a curated BLASTP cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of: single resistance variants, insertions, deletions, co-dependent resistance variants, nonsense SNPs, and/or frameshift mutations. Protein variant model matches to reference sequences are categorized on two criteria: strict and loose. A strict match has a BLASTP bitscore above the curated BLASTP cutoff value and contains at least one detected mutation from amongst the mapped resistance variants; a loose match has a BLASTP bitscore below the curated BLASTP cutoff value but still contains at least one detected mutation from amongst the mapped resistance variants. Regardless of BLASTP bitscore, if a sequence does not contain one of the mapped resistance variants, it is not considered a match and not detected by the protein variant model.

Legend:

  • discovered in clinical, agricultural, or environmental isolates
  • discovered via laboratory selection experiments


Bit-score Cut-off (blastP): 800

PMID: 17294000R13C V18A
PMID: 24855126V18A A300P
PMID: 26104204T110A R268H
PMID: 26369965G313R
PMID: 26311839V18A L50V A300P

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



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