Mycobacterium tuberculosis ethA mutations conferring resistance to prothionamide

Accession ARO:3005106
Synonym(s)Rv3854c
CARD Short NameMtub_ethA_PTO
DefinitionMutations in Mycobacterium tuberculosis ethA conferring resistance to prothionamide, an analogue to isoniazid.
AMR Gene Familyprothionamide resistant ethA
Drug Classthioamide antibiotic
Resistance Mechanismantibiotic target alteration
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic prothionamide [Antibiotic]
+ prothionamide resistant ethA [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 ethA mutations conferring resistance to prothionamide 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

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
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): 1000

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
+nt11:ainsertion mutation from nucleotide sequencePMID:30583053no datano datano data
P28Ssingle resistance variantPMID:30583053no datano datano data
-nt34:gdeletion mutation from nucleotide sequencePMID:30583053no datano datano data
L35Rsingle resistance variantPMID:30583053no datano datano data
G42Dsingle resistance variantPMID:30583053no datano datano data
D56Ysingle resistance variantPMID:30583053no datano datano data
D58Gsingle resistance variantPMID:30583053no datano datano data
W69Csingle resistance variantPMID:30583053no datano datano data
H102Psingle resistance variantPMID:30583053no datano datano data
Y141Nsingle resistance variantPMID:30583053no datano datano data
I161V,G324Rmultiple resistance variantsPMID:30583053no datano datano data
V179Fsingle resistance variantPMID:30583053no datano datano data
T186Psingle resistance variantPMID:30583053no datano datano data
T189Rsingle resistance variantPMID:30583053no datano datano data
+nt213:ainsertion mutation from nucleotide sequencePMID:30583053no datano datano data
R239Q,S266Rmultiple resistance variantsPMID:30583053no datano datano data
Q246R,L446Pmultiple resistance variantsPMID:30583053no datano datano data
Q246Psingle resistance variantPMID:30583053no datano datano data
Q254P,S266Rmultiple resistance variantsPMID:30583053no datano datano data
Q254Psingle resistance variantPMID:30583053no datano datano data
S266R,M373Tmultiple resistance variantsPMID:30583053no datano datano data
S266R,P454Lmultiple resistance variantsPMID:30583053no datano datano data
L267Vsingle resistance variantPMID:30583053no datano datano data
R279Ternonsense mutationPMID:30583053no datano datano data
W289Ternonsense mutationPMID:30583053no datano datano data
S329Psingle resistance variantPMID:30583053no datano datano data
A341Vsingle resistance variantPMID:30583053no datano datano data
+nt342:ainsertion mutation from nucleotide sequencePMID:30583053no datano datano data
N345Ksingle resistance variantPMID:30583053no datano datano data
A352Esingle resistance variantPMID:30583053no datano datano data
M372Rsingle resistance variantPMID:30583053no datano datano data
-nt385:adeletion mutation from nucleotide sequencePMID:30583053no datano datano data
A395Dsingle resistance variantPMID:30583053no datano datano data
C403Ysingle resistance variantPMID:30583053no datano datano data
E420Ternonsense mutationPMID:30583053no datano datano data
-nt455:cdeletion mutation from nucleotide sequencePMID:30583053no datano datano data
F480Ssingle resistance variantPMID:30583053no datano datano data
+nt672:ginsertion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt673:ginsertion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt697:tdeletion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt751:adeletion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt755:cinsertion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt756:cinsertion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt757:cinsertion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt797:ginsertion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt822:gdeletion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt884:tdeletion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt1033:adeletion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt1043:tdeletion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt1133:cdeletion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt1219:ainsertion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt1247:ainsertion mutation from nucleotide sequencePMID:30583053no datano datano data
+nt1336:cinsertion mutation from nucleotide sequencePMID:30583053no datano datano data
-nt1339:cdeletion mutation from nucleotide sequencePMID:30583053no datano datano data

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



>gb|NC_000962.3|-|4326004-4327473|Mycobacterium tuberculosis ethA mutations conferring resistance to prothionamide [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