Mycobacterium tuberculosis mshA mutations conferring resistance to isoniazid

Accession ARO:3004925
Synonym(s)Rv0486
CARD Short NameMtub_mshA_INH
DefinitionMutations that occur in Mycobacterium tuberculosis mshA that result in or contribute to antibiotic resistance to isoniazid.
AMR Gene Familyisoniazid resistant mshA
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 mshA [AMR Gene Family]
Publications

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)

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 mshA mutations 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

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
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): 875

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 30583053F355S
PMID: 30337678N111S A187V L306R T334A

ReSeqTB:

Minimal ConfidenceA187V
Indeterminate ConfidenceT334A L306R

>gb|NP_215000.1|+|Mycobacterium tuberculosis mshA mutations conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
MAGVRHDDGSGLIAQRRPVRGEGATRSRGPSGPSNRNVSAADDPRRVALLAVHTSPLAQP
GTGDAGGMNVYMLQSALHLARRGIEVEIFTRATASADPPVVRVAPGVLVRNVVAGPFEGL
DKYDLPTQLCAFAAGVLRAEAVHEPGYYDIVHSHYWLSGQVGWLARDRWAVPLVHTAHTL
AAVKNAALADGDGPEPPLRTVGEQQVVDEADRLIVNTDDEARQVISLHGADPARIDVVHP
GVDLDVFRPGDRRAARAALGLPVDERVVAFVGRIQPLKAPDIVLRAAAKLPGVRIIVAGG
PSGSGLASPDGLVRLADELGISARVTFLPPQSHTDLATLFRAADLVAVPSYSESFGLVAV
EAQACGTPVVAAAVGGLPVAVRDGITGTLVSGHEVGQWADAIDHLLRLCAGPRGRVMSRA
AARHAATFSWENTTDALLASYRRAIGEYNAERQRRGGEVISDLVAVGKPRHWTPRRGVGA



>gb|NC_000962.3|+|575348-576790|Mycobacterium tuberculosis mshA mutations conferring resistance to isoniazid [Mycobacterium tuberculosis H37Rv]
ATGGCAGGTGTGCGGCACGATGACGGTTCAGGGTTGATCGCCCAGCGCCGTCCGGTCCGCGGCGAGGGTGCCACCCGCTCGCGCGGCCCA
TCCGGGCCATCCAATCGGAATGTTTCGGCAGCAGACGACCCGCGCCGGGTTGCGCTGCTGGCGGTGCACACCTCACCGCTGGCACAGCCG
GGCACCGGTGACGCCGGCGGCATGAACGTCTACATGCTGCAAAGTGCGCTGCACCTGGCCCGTCGGGGCATCGAGGTGGAGATCTTCACC
CGGGCCACCGCATCGGCAGATCCACCGGTGGTGCGGGTGGCACCCGGGGTGCTGGTGCGCAACGTGGTGGCGGGGCCCTTCGAGGGTTTG
GACAAGTACGACCTGCCCACCCAGCTTTGTGCGTTCGCCGCCGGGGTGCTGCGCGCCGAGGCGGTCCACGAACCGGGTTACTACGACATC
GTGCACTCGCACTACTGGCTGTCGGGTCAGGTCGGCTGGCTGGCGCGCGACCGCTGGGCGGTGCCGTTGGTGCACACCGCACACACGCTG
GCCGCCGTGAAGAACGCGGCACTGGCCGACGGCGACGGACCCGAGCCGCCGCTGCGTACGGTCGGGGAGCAGCAGGTCGTCGACGAGGCG
GATCGGTTGATCGTCAACACCGACGATGAAGCCAGGCAAGTGATTTCGCTTCATGGTGCCGATCCGGCACGAATCGACGTGGTCCATCCC
GGTGTCGATCTGGACGTGTTCCGCCCGGGTGATCGGCGCGCGGCCCGGGCCGCGCTAGGACTACCAGTTGACGAGCGCGTGGTGGCCTTC
GTCGGACGCATCCAGCCGCTGAAGGCACCCGACATTGTGCTGCGTGCGGCCGCCAAGTTGCCCGGGGTGCGCATCATCGTGGCCGGCGGA
CCGTCGGGCAGCGGTCTGGCTTCACCGGACGGACTGGTCCGGCTCGCCGACGAACTGGGCATCTCTGCACGGGTGACGTTTCTGCCGCCG
CAGTCCCACACGGATCTGGCCACCTTGTTTCGGGCGGCGGACCTGGTTGCGGTGCCGAGCTACTCCGAGTCGTTCGGCCTGGTTGCTGTG
GAGGCCCAAGCGTGCGGCACACCGGTGGTGGCCGCGGCGGTGGGCGGGCTGCCCGTCGCGGTGCGCGACGGGATCACCGGCACCCTGGTG
TCCGGGCACGAGGTCGGTCAGTGGGCCGACGCCATCGATCACCTGCTGCGGTTGTGTGCCGGGCCACGGGGACGGGTGATGAGCCGGGCG
GCGGCACGGCACGCCGCCACGTTCTCGTGGGAGAACACCACCGACGCGCTGTTGGCCAGTTATCGGCGTGCGATCGGCGAGTACAACGCC
GAGCGCCAGCGCCGGGGCGGCGAGGTGATATCGGACCTGGTAGCGGTGGGCAAGCCCCGCCACTGGACGCCGCGTCGCGGGGTGGGCGCG
TGA