Mycobacterium tuberculosis ethA with mutation conferring resistance to ethionamide

Accession ARO:3003458
CARD Short NameMtub_ethA_ETO
DefinitionSpecific mutations that occurs on Mycobacterium tuberculosis ethA causing it to be ethionamide resistant.
AMR Gene Familyethionamide resistant ethA
Drug Classthioamide antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium marinumg+wgs, Mycobacterium tuberculosisg+wgs
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ ethionamide resistant ethA [AMR Gene Family]
+ confers_resistance_to_antibiotic ethionamide [Antibiotic]
Publications

Morlock GP, et al. 2003. Antimicrob Agents Chemother 47(12): 3799-3805. ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. (PMID 14638486)

DeBarber AE, et al. 2000. Proc. Natl. Acad. Sci. U.S.A. 97(17):9677-82 Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. (PMID 10944230)

de Welzen L, et al. 2017. Antimicrob. Agents Chemother. 61(12): Whole-Transcriptome and -Genome Analysis of Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates Identifies Downregulation ofas a Mechanism of Ethionamide Resistance. (PMID 28993337)

Resistomes

Prevalence of Mycobacterium tuberculosis ethA with mutation conferring resistance to ethionamide 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 marinum85.71%0%77.36%0%
Mycobacterium tuberculosis0.82%0%0.8%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): 900

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID in progress (TB): A11G G11fs Y147STOP H281P N379D P422fs

PMID: 14638486G43S D55A E223K I338S G385D T392A G413D R463S -nt110:A -nt1290:C +nt338:A -nt65:1 -nt703:T -nt768:G +nt811:1
PMID: 10944230G43C P51L D58A Y84D T186K T342K A381P
PMID: 28993337ntT-11C

ReSeqTB:

High ConfidenceT342K N379D P422fs G11fs Y147STOP H281P A11G

>gb|AAK48336.1|-|Mycobacterium tuberculosis ethA with mutation conferring resistance to ethionamide [Mycobacterium tuberculosis CDC1551]
MTEHLDVVIVGAGISGVSAAWHLQDRCPTKSYAILEKRESMGGTWDLFRYPGIRSDSDMY
TLGFRFRPWTGRQAIADGKPILEYVKSTAAMYGIDRHIRFHHKVISADWSTAENRWTVHI
QSHGTLSALTCEFLFLCSGYYNYDEGYSPRFAGSEDFVGPIIHPQHWPEDLDYDAKNIVV
IGSGATAVTLVPALADSGAKHVTMLQRSPTYIVSQPDRDGIAEKLNRWLPETMAYTAVRW
KNVLRQAAVYSACQKWPRRMRKMFLSLIQRQLPEGYDVRKHFGPHYNPWDQRLCLVPNGD
LFRAIRHGKVEVVTDTIERFTATGIRLNSGRELPADIIITATGLNLQLFGGATATIDGQQ
VDITTTMAYKGMMLSGIPNMAYTVGYTNASWTLKADLVSEFVCRLLNYMDDNGFDTVVVE
RPGSDVEERPFMEFTPGYVLRSLDELPKQGSRTPWRLNQNYLRDIRLIRRGKIDDEGLRF
AKRPAPVGV



>gb|AE000516.2|-|4318328-4319797|Mycobacterium tuberculosis ethA with mutation conferring resistance to ethionamide [Mycobacterium tuberculosis CDC1551]
ATGACCGAGCACCTCGACGTTGTCATCGTGGGCGCTGGAATCTCCGGTGTCAGCGCGGCCTGGCACCTGCAGGACCGTTGCCCGACCAAG
AGCTACGCCATCCTGGAAAAGCGGGAATCCATGGGCGGCACCTGGGATTTGTTCCGTTATCCCGGAATTCGCTCCGACTCCGACATGTAC
ACGCTAGGTTTCCGATTCCGTCCCTGGACCGGACGGCAGGCGATCGCCGACGGCAAGCCCATCCTCGAGTACGTCAAGAGCACCGCGGCC
ATGTATGGAATCGACAGGCATATCCGGTTCCACCACAAGGTGATCAGTGCCGATTGGTCGACCGCGGAAAACCGCTGGACCGTTCACATC
CAAAGCCACGGCACGCTCAGCGCCCTCACCTGCGAATTCCTCTTTCTGTGCAGCGGCTACTACAACTACGACGAGGGCTACTCGCCGAGA
TTCGCCGGCTCGGAGGATTTCGTCGGGCCGATCATCCATCCGCAGCACTGGCCCGAGGACCTCGACTACGACGCTAAGAACATCGTCGTG
ATCGGCAGTGGCGCAACGGCGGTCACGCTCGTGCCGGCGCTGGCGGACTCGGGCGCCAAGCACGTCACGATGCTGCAGCGCTCACCCACC
TACATCGTGTCGCAGCCAGACCGGGACGGCATCGCCGAGAAGCTCAACCGCTGGCTGCCGGAGACCATGGCCTACACCGCGGTACGGTGG
AAGAACGTGCTGCGCCAGGCGGCCGTGTACAGCGCCTGCCAGAAGTGGCCACGGCGCATGCGGAAGATGTTCCTGAGCCTGATCCAGCGC
CAGCTACCCGAGGGGTACGACGTGCGAAAGCACTTCGGCCCGCACTACAACCCCTGGGACCAGCGATTGTGCTTGGTGCCCAACGGCGAC
CTGTTCCGGGCCATTCGTCACGGGAAGGTCGAGGTGGTGACCGACACCATTGAACGGTTCACCGCGACCGGAATCCGGCTGAACTCAGGT
CGCGAACTGCCGGCTGACATCATCATTACCGCAACGGGGTTGAACCTGCAGCTTTTTGGTGGGGCGACGGCGACTATCGACGGACAACAA
GTGGACATCACCACGACGATGGCCTACAAGGGCATGATGCTTTCCGGCATCCCCAACATGGCCTACACGGTTGGCTACACCAATGCCTCC
TGGACGCTGAAGGCCGACCTGGTGTCGGAGTTTGTCTGTCGCTTGTTGAATTACATGGACGACAACGGTTTTGACACCGTGGTCGTCGAG
CGACCGGGCTCAGATGTCGAAGAGCGGCCCTTCATGGAGTTCACCCCAGGTTACGTGCTGCGCTCGCTGGACGAGCTGCCCAAGCAGGGT
TCGCGTACACCGTGGCGCCTGAATCAGAACTACCTACGTGACATCCGGCTCATCCGGCGCGGCAAGATCGACGACGAGGGTCTGCGGTTC
GCCAAAAGGCCTGCCCCGGTGGGGGTTTAG