Mycobacterium tuberculosis ethA with mutation conferring resistance to ethionamide

Download Sequences
Accession ARO:3003458
Synonym(s)Rv3854c
CARD Short NameMtub_ethA_ETO
DefinitionMycobacterium tuberculosis ethA (Rv3854c) is a mono-oxygenase enzyme which activates the antibiotic ethionamide in vivo. Mutations in ethA confer resistance to ethionamide by modulating the activation and activity of the ethionamide prodrug.
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)

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)

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 ethA with mutation conferring resistance to ethionamide 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 (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
Mycobacterium marinum85.71%0%84.91%0%0%
Mycobacterium tuberculosis0.82%0%1.61%0%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

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
M1Varsingle resistance variantno datano datano dataWHO-R
t-7csnp in promoter regionno datano datano dataWHO-R
t-11csnp in promoter regionPMID:28993337no datano datano data
G11fsframeshift mutationno dataReSeqTB-Highno datano data
W21Ternonsense mutationno datano datano dataWHO-R
Q24Ternonsense mutationno datano datano dataWHO-R
Y32Ternonsense mutationno datano datano dataWHO-R
L35Rsingle resistance variantno datano datano dataWHO-R
G43Ssingle resistance variantPMID:14638486no datano dataWHO-U
G43Csingle resistance variantPMID:10944230no datano datano data
W45Ternonsense mutationno datano datano dataWHO-R
P51Lsingle resistance variantPMID:10944230no datano dataWHO-U
S57Ysingle resistance variantno datano datano dataWHO-R
D58Asingle resistance variantPMID:10944230no datano datano data
Y60Ternonsense mutationno datano datano dataWHO-R
R65Ternonsense mutationno datano datano dataWHO-R
-nt65:1deletion mutation from nucleotide sequencePMID:14638486no datano datano data
W69Ternonsense mutationno datano datano dataWHO-R
Q73Ternonsense mutationno datano datano dataWHO-R
Y84Ternonsense mutationno datano datano dataWHO-R
Y84Dsingle resistance variantPMID:10944230no datano dataWHO-U
K86Ternonsense mutationno datano datano dataWHO-R
T88Isingle resistance variantno datano datano dataWHO-R
Y92Ternonsense mutationno datano datano dataWHO-R
K103Ternonsense mutationno datano datano dataWHO-R
W109Ternonsense mutationno datano datano dataWHO-R
-nt110:adeletion mutation from nucleotide sequencePMID:14638486no datano datano data
W116Ternonsense mutationno datano datano dataWHO-R
Q121Ternonsense mutationno datano datano dataWHO-R
C131Ternonsense mutationno datano datano dataWHO-R
E132Ternonsense mutationno datano datano dataWHO-R
Y140Ternonsense mutationno datano datano dataWHO-R
Y143Ternonsense mutationno datano datano dataWHO-R
Y147Ternonsense mutationno dataReSeqTB-Highno dataWHO-R
E155Ternonsense mutationno datano datano dataWHO-R
Q165Ternonsense mutationno datano datano dataWHO-R
W167Ternonsense mutationno datano datano dataWHO-R
T186Ksingle resistance variantPMID:10944230no datano datano data
S197Ternonsense mutationno datano datano dataWHO-R
V202Gsingle resistance variantno datano datano dataWHO-R
Q206Ternonsense mutationno datano datano dataWHO-R
R207Gsingle resistance variantno datano datano dataWHO-R
S208Ternonsense mutationno datano datano dataWHO-R
Y211Ternonsense mutationno datano datano dataWHO-R
Q215Ternonsense mutationno datano datano dataWHO-R
E223Ksingle resistance variantPMID:14638486no datano datano data
W228Ternonsense mutationno datano datano dataWHO-R
W240Ternonsense mutationno datano datano dataWHO-R
K241Ternonsense mutationno datano datano dataWHO-R
Q246Ternonsense mutationno datano datano dataWHO-R
Y250Ternonsense mutationno datano datano dataWHO-R
C253Ternonsense mutationno datano datano dataWHO-R
Q254Ternonsense mutationno datano datano dataWHO-R
W256Ternonsense mutationno datano datano dataWHO-R
Q269Ternonsense mutationno datano datano dataWHO-R
Q271Ternonsense mutationno datano datano dataWHO-R
Y276Ternonsense mutationno datano datano dataWHO-R
R279Ternonsense mutationno datano datano dataWHO-R
H281Psingle resistance variantno dataReSeqTB-Highno dataWHO-U
W289Ternonsense mutationno datano datano dataWHO-R
Q291Ternonsense mutationno datano datano dataWHO-R
R292Ternonsense mutationno datano datano dataWHO-R
L293Ternonsense mutationno datano datano dataWHO-R
C294Ternonsense mutationno datano datano dataWHO-R
E332Ternonsense mutationno datano datano dataWHO-R
I338Ssingle resistance variantPMID:14638486no datano datano data
+nt338:ainsertion mutation from nucleotide sequencePMID:14638486no datano datano data
A341Vsingle resistance variantno datano datano dataWHO-R
T342Ksingle resistance variantPMID:10944230ReSeqTB-Highno dataWHO-U
Q347Ternonsense mutationno datano datano dataWHO-R
Q359Ternonsense mutationno datano datano dataWHO-R
Q360Ternonsense mutationno datano datano dataWHO-R
Y369Ternonsense mutationno datano datano dataWHO-R
N379Dsingle resistance variantno dataReSeqTB-Highno dataWHO-R
A381Psingle resistance variantPMID:10944230no datano dataWHO-U
Y382Ternonsense mutationno datano datano dataWHO-R
G385Dsingle resistance variantPMID:14638486no datano datano data
Y386Ternonsense mutationno datano datano dataWHO-R
S390Fsingle resistance variantno datano datano dataWHO-R
W391Ternonsense mutationno datano datano dataWHO-R
T392Asingle resistance variantPMID:14638486no datano datano data
K394Ternonsense mutationno datano datano dataWHO-R
S399Ternonsense mutationno datano datano dataWHO-R
C403Ysingle resistance variantno datano datano dataWHO-R
Y408Ternonsense mutationno datano datano dataWHO-R
G413Dsingle resistance variantPMID:14638486no datano datano data
R421Ternonsense mutationno datano datano dataWHO-R
P422fsframeshift mutationno dataReSeqTB-Highno datano data
E427Ternonsense mutationno datano datano dataWHO-R
Y438Ternonsense mutationno datano datano dataWHO-R
Q449Ternonsense mutationno datano datano dataWHO-R
W455Ternonsense mutationno datano datano dataWHO-R
Y461Ternonsense mutationno datano datano dataWHO-R
R463Ssingle resistance variantPMID:14638486no datano datano data
E476Ternonsense mutationno datano datano dataWHO-R
-nt703:tdeletion mutation from nucleotide sequencePMID:14638486no datano datano data
-nt768:gdeletion mutation from nucleotide sequencePMID:14638486no datano datano data
+nt811:1insertion mutation from nucleotide sequencePMID:14638486no datano datano data
-nt1290:cdeletion mutation from nucleotide sequencePMID:14638486no datano datano data

>gb|NP_218371.1|-|Mycobacterium tuberculosis ethA with mutation conferring resistance to ethionamide [Mycobacterium tuberculosis H37Rv]
MTEHLDVVIVGAGISGVSAAWHLQDRCPTKSYAILEKRESMGGTWDLFRYPGIRSDSDMY
TLGFRFRPWTGRQAIADGKPILEYVKSTAAMYGIDRHIRFHHKVISADWSTAENRWTVHI
QSHGTLSALTCEFLFLCSGYYNYDEGYSPRFAGSEDFVGPIIHPQHWPEDLDYDAKNIVV
IGSGATAVTLVPALADSGAKHVTMLQRSPTYIVSQPDRDGIAEKLNRWLPETMAYTAVRW
KNVLRQAAVYSACQKWPRRMRKMFLSLIQRQLPEGYDVRKHFGPHYNPWDQRLCLVPNGD
LFRAIRHGKVEVVTDTIERFTATGIRLNSGRELPADIIITATGLNLQLFGGATATIDGQQ
VDITTTMAYKGMMLSGIPNMAYTVGYTNASWTLKADLVSEFVCRLLNYMDDNGFDTVVVE
RPGSDVEERPFMEFTPGYVLRSLDELPKQGSRTPWRLNQNYLRDIRLIRRGKIDDEGLRF
AKRPAPVGV


>gb|NC_000962.3|-|4326004-4327473|Mycobacterium tuberculosis ethA with mutation conferring resistance to ethionamide [Mycobacterium tuberculosis H37Rv]
ATGACCGAGCACCTCGACGTTGTCATCGTGGGCGCTGGAATCTCCGGTGTCAGCGCGGCCTGGCACCTGCAGGACCGTTGCCCGACCAAG
AGCTACGCCATCCTGGAAAAGCGGGAATCCATGGGCGGCACCTGGGATTTGTTCCGTTATCCCGGAATTCGCTCCGACTCCGACATGTAC
ACGCTAGGTTTCCGATTCCGTCCCTGGACCGGACGGCAGGCGATCGCCGACGGCAAGCCCATCCTCGAGTACGTCAAGAGCACCGCGGCC
ATGTATGGAATCGACAGGCATATCCGGTTCCACCACAAGGTGATCAGTGCCGATTGGTCGACCGCGGAAAACCGCTGGACCGTTCACATC
CAAAGCCACGGCACGCTCAGCGCCCTCACCTGCGAATTCCTCTTTCTGTGCAGCGGCTACTACAACTACGACGAGGGCTACTCGCCGAGA
TTCGCCGGCTCGGAGGATTTCGTCGGGCCGATCATCCATCCGCAGCACTGGCCCGAGGACCTCGACTACGACGCTAAGAACATCGTCGTG
ATCGGCAGTGGCGCAACGGCGGTCACGCTCGTGCCGGCGCTGGCGGACTCGGGCGCCAAGCACGTCACGATGCTGCAGCGCTCACCCACC
TACATCGTGTCGCAGCCAGACCGGGACGGCATCGCCGAGAAGCTCAACCGCTGGCTGCCGGAGACCATGGCCTACACCGCGGTACGGTGG
AAGAACGTGCTGCGCCAGGCGGCCGTGTACAGCGCCTGCCAGAAGTGGCCACGGCGCATGCGGAAGATGTTCCTGAGCCTGATCCAGCGC
CAGCTACCCGAGGGGTACGACGTGCGAAAGCACTTCGGCCCGCACTACAACCCCTGGGACCAGCGATTGTGCTTGGTGCCCAACGGCGAC
CTGTTCCGGGCCATTCGTCACGGGAAGGTCGAGGTGGTGACCGACACCATTGAACGGTTCACCGCGACCGGAATCCGGCTGAACTCAGGT
CGCGAACTGCCGGCTGACATCATCATTACCGCAACGGGGTTGAACCTGCAGCTTTTTGGTGGGGCGACGGCGACTATCGACGGACAACAA
GTGGACATCACCACGACGATGGCCTACAAGGGCATGATGCTTTCCGGCATCCCCAACATGGCCTACACGGTTGGCTACACCAATGCCTCC
TGGACGCTGAAGGCCGACCTGGTGTCGGAGTTTGTCTGTCGCTTGTTGAATTACATGGACGACAACGGTTTTGACACCGTGGTCGTCGAG
CGACCGGGCTCAGATGTCGAAGAGCGGCCCTTCATGGAGTTCACCCCAGGTTACGTGCTGCGCTCGCTGGACGAGCTGCCCAAGCAGGGT
TCGCGTACACCGTGGCGCCTGAATCAGAACTACCTACGTGACATCCGGCTCATCCGGCGCGGCAAGATCGACGACGAGGGTCTGCGGTTC
GCCAAAAGGCCTGCCCCGGTGGGGGTTTAG

Curator Acknowledgements
Curator Description Most Recent Edit