| Accession | ARO:3003326 |
| Synonym(s) | Rv3795 |
| CARD Short Name | Mtub_embB_EMB |
| Definition | Point mutations that occur within Mycobacterium tuberculosis embB gene resulting in resistance to ethambutol. |
| AMR Gene Family | ethambutol resistant embB |
| Drug Class | polyamine antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Mycobacterium tuberculosisg+wgs |
| Classification | 10 ontology terms | Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + determinant of antibiotic resistance + antibiotic molecule + polyamine antibiotic [Drug Class] + antibiotic resistant gene variant or mutant + antibiotic-resistant emb arabinosyltransferase + ethambutol [Antibiotic] |
| Parent Term(s) | 2 ontology terms | Show + ethambutol resistant embB [AMR Gene Family] + confers_resistance_to_antibiotic ethambutol [Antibiotic] |
| Publications | Campbell PJ, et al. 2011. Antimicrob Agents Chemother 55(5): 2032-2041. Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. (PMID 21300839) Shi D, et al. 2011. J Antimicrob Chemother 66(10): 2240-2247. Characteristics of embB mutations in multidrug-resistant Mycobacterium tuberculosis isolates in Henan, China. (PMID 21778195) Bakula Z, et al. 2014. Biomed Res Int 2013: 167954. Mutations in the embB gene and their association with ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates from Poland. (PMID 24392447) Srivastava S, et al. 2006. Curr Microbiol 53(5): 401-405. Nucleotide polymorphism associated with ethambutol resistance in clinical isolates of Mycobacterium tuberculosis. (PMID 16972132) Plinke C, et al. 2006. Antimicrob Agents Chemother 50(5): 1900-1902. Significance of mutations in embB codon 306 for prediction of ethambutol resistance in clinical Mycobacterium tuberculosis isolates. (PMID 16641474) Lee HY, et al. 2002. Yonsei Med J 43(1): 59-64. Mutations in the embB locus among Korean clinical isolates of Mycobacterium tuberculosis resistant to ethambutol. (PMID 11854934) Sugawara I, et al. 2005. Jpn J Infect Dis 58(6): 393-395. The molecular epidemiology of ethambutol-resistant Mycobacterium tuberculosis in Henan Province, China. (PMID 16377878) Ramaswamy SV, et al. 2000. Antimicrob Agents Chemother 44(2): 326-336. Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis. (PMID 10639358) Chan RC, et al. 2007. J Antimicrob Chemother 59(5): 866-873. Genetic and phenotypic characterization of drug-resistant Mycobacterium tuberculosis isolates in Hong Kong. (PMID 17360809) Sreevatsan S, et al. 1997. Antimicrob Agents Chemother 41(8): 1677-1681. Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations. (PMID 9257740) Telenti A, et al. 1997. Nat Med 3(5): 567-570. The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. (PMID 9142129) 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) The CRyPTIC Consortium 2022. PLoS Biol 20(8):e3001721 A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics. (PMID 35944069) 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) |
Prevalence of Mycobacterium tuberculosis embB mutant conferring resistance to ethambutol 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).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI | GRDI-AMR2 |
|---|---|---|---|---|---|
| Mycobacterium tuberculosis | 54.3% | 0% | 41.86% | 0% | 0% |
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): 2000
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).| Mutation | Mutation type | PubMed | ReSeqTB | CRyPTIC | WHO |
|---|---|---|---|---|---|
| S22C | single resistance variant | no data | ReSeqTB-High | no data | no data |
| L239P | single resistance variant | PMID:16972132 | no data | no data | no data |
| D240H | single resistance variant | PMID:16972132 | no data | no data | no data |
| N296H | single resistance variant | no data | ReSeqTB-High | no data | no data |
| S297A | single resistance variant | PMID:10639358 | no data | no data | no data |
| D299E | single resistance variant | PMID:16972132 | no data | no data | no data |
| M306I | single resistance variant | PMID:21300839 | ReSeqTB-Moderate | CRyPTIC-R | WHO-R |
| M306T | single resistance variant | PMID:11854934 | no data | no data | no data |
| M306L | single resistance variant | PMID:16641474 | ReSeqTB-Minimal | CRyPTIC-S | WHO-R |
| M306V | single resistance variant | PMID:21300839 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| M306Var | single resistance variant | no data | no data | CRyPTIC-R | no data |
| D311H | single resistance variant | PMID:16972132 | no data | no data | no data |
| A314G,Y322C | multiple resistance variants | PMID:11854934 | no data | no data | no data |
| Y319C | single resistance variant | PMID:16377878 | ReSeqTB-High | no data | WHO-R |
| Y319N | single resistance variant | PMID:17360809 | no data | no data | no data |
| Y319S | single resistance variant | no data | ReSeqTB-High | no data | WHO-R |
| D328G | single resistance variant | PMID:10639358 | no data | no data | no data |
| D328Y | single resistance variant | PMID:10639358 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| F330V | single resistance variant | PMID:10639358 | no data | no data | no data |
| F330S | single resistance variant | no data | ReSeqTB-High | no data | WHO-U |
| Y333C | single resistance variant | PMID:16377878 | no data | no data | no data |
| Y334H | single resistance variant | PMID:10639358 | ReSeqTB-High | no data | no data |
| S347I | single resistance variant | no data | ReSeqTB-Moderate | no data | WHO-U |
| D354A | single resistance variant | no data | ReSeqTB-Moderate | CRyPTIC-R | WHO-R |
| E368A | single resistance variant | PMID:16972132 | no data | no data | no data |
| P375A | single resistance variant | curation underway | no data | no data | no data |
| E378A | single resistance variant | PMID:16972132 | ReSeqTB-None | CRyPTIC-S | WHO-S |
| S380R | single resistance variant | PMID:16972132 | no data | no data | no data |
| P397Q | single resistance variant | PMID:16972132 | no data | no data | no data |
| N399H | single resistance variant | curation underway | no data | no data | no data |
| L402V | single resistance variant | no data | ReSeqTB-High | no data | no data |
| G406S | single resistance variant | PMID:10639358 | ReSeqTB-Moderate | CRyPTIC-R | WHO-R |
| G406D | single resistance variant | PMID:10639358 | ReSeqTB-Minimal | CRyPTIC-R | WHO-R |
| G406A | single resistance variant | PMID:10639358 | ReSeqTB-Moderate | CRyPTIC-R | WHO-R |
| G406C | single resistance variant | PMID:10639358 | ReSeqTB-High | no data | WHO-R |
| L413P | single resistance variant | PMID:24392447 | no data | no data | no data |
| P446H | single resistance variant | PMID:16972132 | no data | no data | no data |
| A454T | single resistance variant | no data | ReSeqTB-High | CRyPTIC-S | no data |
| R460C | single resistance variant | curation underway | no data | no data | no data |
| I465D | single resistance variant | PMID:16972132 | no data | no data | no data |
| R469P | single resistance variant | PMID:16972132 | no data | no data | no data |
| R471P | single resistance variant | PMID:16972132 | no data | no data | no data |
| Q497R | single resistance variant | PMID:10639358 | ReSeqTB-High | CRyPTIC-R | WHO-R |
| Q497K | single resistance variant | PMID:10639358 | ReSeqTB-Minimal | CRyPTIC-R | WHO-R |
| E504Q | single resistance variant | PMID:24392447 | no data | no data | no data |
| R507G | single resistance variant | PMID:24392447 | no data | no data | no data |
| T630I | single resistance variant | PMID:9257740 | no data | no data | no data |
| G745D | single resistance variant | PMID:10639358 | no data | no data | no data |
| D959A | single resistance variant | PMID:10639358 | no data | no data | no data |
| M1000R | single resistance variant | PMID:10639358 | no data | no data | WHO-U |
| D1024N | single resistance variant | PMID:10639358 | ReSeqTB-Minimal | CRyPTIC-S | no data |
| N1033K | single resistance variant | no data | no data | CRyPTIC-R | no data |
| Curator | Description | Most Recent Edit |
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