Mycobacterium tuberculosis embB mutant conferring resistance to ethambutol

Accession ARO:3003326
Synonym(s)Rv3795
CARD Short NameMtub_embB_EMB
DefinitionPoint mutations that occur within Mycobacterium tuberculosis embB gene resulting in resistance to ethambutol.
AMR Gene Familyethambutol resistant embB
Drug Classpolyamine antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification10 ontology terms | Show
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)

Resistomes

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 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 tuberculosis54.3%0%26.92%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): 2000

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID in progress (single): P375A N399H R460C

PMID: 21300839M306V M306I
PMID: 21778195G406A G406D Q497R
PMID: 24392447L413P E504Q R507G
PMID: 16972132L239P D240H D299E D311H E368A E378A S380R P397Q P446H I465D R469P R471P
PMID: 16641474M306L
PMID: 11854934M306T A314G,Y322C
PMID: 16377878Y319C Y333C
PMID: 10639358S297A D328G D328Y F330V Y334H G406C G406A G406D G406S Q497K Q497R G745D D959A M1000R D1024N
PMID: 17360809Y319N
PMID: 9257740T630I
PMID: 30337678N13S S22C L172R R213Q N296H M306I M306L M306V Y319C Y319S D328Y F330S Y334H S347I D354A E378A L402V G406A G406C G406D G406S A454T Q497K Q497R D1024N

ReSeqTB:

High ConfidenceY334H L402V G406C A454T Q497R S22C N296H M306V Y319S Y319C D328Y F330S
Moderate ConfidenceS347I D354A G406S G406A M306I
Minimal ConfidenceG406D Q497K D1024N M306L
Indeterminate ConfidenceN13S R213Q

>gb|NP_218312.1|+|Mycobacterium tuberculosis embB mutant conferring resistance to ethambutol [Mycobacterium tuberculosis H37Rv]
MTQCASRRKSTPNRAILGAFASARGTRWVATIAGLIGFVLSVATPLLPVVQTTAMLDWPQ
RGQLGSVTAPLISLTPVDFTATVPCDVVRAMPPAGGVVLGTAPKQGKDANLQALFVVVSA
QRVDVTDRNVVILSVPREQVTSPQCQRIEVTSTHAGTFANFVGLKDPSGAPLRSGFPDPN
LRPQIVGVFTDLTGPAPPGLAVSATIDTRFSTRPTTLKLLAIIGAIVATVVALIALWRLD
QLDGRGSIAQLLLRPFRPASSPGGMRRLIPASWRTFTLTDAVVIFGFLLWHVIGANSSDD
GYILGMARVADHAGYMSNYFRWFGSPEDPFGWYYNLLALMTHVSDASLWMRLPDLAAGLV
CWLLLSREVLPRLGPAVEASKPAYWAAAMVLLTAWMPFNNGLRPEGIIALGSLVTYVLIE
RSMRYSRLTPAALAVVTAAFTLGVQPTGLIAVAALVAGGRPMLRILVRRHRLVGTLPLVS
PMLAAGTVILTVVFADQTLSTVLEATRVRAKIGPSQAWYTENLRYYYLILPTVDGSLSRR
FGFLITALCLFTAVFIMLRRKRIPSVARGPAWRLMGVIFGTMFFLMFTPTKWVHHFGLFA
AVGAAMAALTTVLVSPSVLRWSRNRMAFLAALFFLLALCWATTNGWWYVSSYGVPFNSAM
PKIDGITVSTIFFALFAIAAGYAAWLHFAPRGAGEGRLIRALTTAPVPIVAGFMAAVFVA
SMVAGIVRQYPTYSNGWSNVRAFVGGCGLADDVLVEPDTNAGFMKPLDGDSGSWGPLGPL
GGVNPVGFTPNGVPEHTVAEAIVMKPNQPGTDYDWDAPTKLTSPGINGSTVPLPYGLDPA
RVPLAGTYTTGAQQQSTLVSAWYLLPKPDDGHPLVVVTAAGKIAGNSVLHGYTPGQTVVL
EYAMPGPGALVPAGRMVPDDLYGEQPKAWRNLRFARAKMPADAVAVRVVAEDLSLTPEDW
IAVTPPRVPDLRSLQEYVGSTQPVLLDWAVGLAFPCQQPMLHANGIAEIPKFRITPDYSA
KKLDTDTWEDGTNGGLLGITDLLLRAHVMATYLSRDWARDWGSLRKFDTLVDAPPAQLEL
GTATRSGLWSPGKIRIGP



>gb|NC_000962.3|+|4246514-4249810|Mycobacterium tuberculosis embB mutant conferring resistance to ethambutol [Mycobacterium tuberculosis H37Rv]
ATGACACAGTGCGCGAGCAGACGCAAAAGCACCCCAAATCGGGCGATTTTGGGGGCTTTTGCGTCTGCTCGCGGGACGCGCTGGGTGGCC
ACCATCGCCGGGCTGATTGGCTTTGTGTTGTCGGTGGCGACGCCGCTGCTGCCCGTCGTGCAGACCACCGCGATGCTCGACTGGCCACAG
CGGGGGCAACTGGGCAGCGTGACCGCCCCGCTGATCTCGCTGACGCCGGTCGACTTTACCGCCACCGTGCCGTGCGACGTGGTGCGCGCC
ATGCCACCCGCGGGCGGGGTGGTGCTGGGCACCGCACCCAAGCAAGGCAAGGACGCCAATTTGCAGGCGTTGTTCGTCGTCGTCAGCGCC
CAGCGCGTGGACGTCACCGACCGCAACGTGGTGATCTTGTCCGTGCCGCGCGAGCAGGTGACGTCCCCGCAGTGTCAACGCATCGAGGTC
ACCTCTACCCACGCCGGCACCTTCGCCAACTTCGTCGGGCTCAAGGACCCGTCGGGCGCGCCGCTGCGCAGCGGCTTCCCCGACCCCAAC
CTGCGCCCGCAGATTGTCGGGGTGTTCACCGACCTGACCGGGCCCGCGCCGCCCGGGCTGGCGGTCTCGGCGACCATCGACACCCGGTTC
TCCACCCGGCCGACCACGCTGAAACTGCTGGCGATCATCGGGGCGATCGTGGCCACCGTCGTCGCACTGATCGCGTTGTGGCGCCTGGAC
CAGTTGGACGGGCGGGGCTCAATTGCCCAGCTCCTCCTCAGGCCGTTCCGGCCTGCATCGTCGCCGGGCGGCATGCGCCGGCTGATTCCG
GCAAGCTGGCGCACCTTCACCCTGACCGACGCCGTGGTGATATTCGGCTTCCTGCTCTGGCATGTCATCGGCGCGAATTCGTCGGACGAC
GGCTACATCCTGGGCATGGCCCGAGTCGCCGACCACGCCGGCTACATGTCCAACTATTTCCGCTGGTTCGGCAGCCCGGAGGATCCCTTC
GGCTGGTATTACAACCTGCTGGCGCTGATGACCCATGTCAGCGACGCCAGTCTGTGGATGCGCCTGCCAGACCTGGCCGCCGGGCTAGTG
TGCTGGCTGCTGCTGTCGCGTGAGGTGCTGCCCCGCCTCGGGCCGGCGGTGGAGGCCAGCAAACCCGCCTACTGGGCGGCGGCCATGGTC
TTGCTGACCGCGTGGATGCCGTTCAACAACGGCCTGCGGCCGGAGGGCATCATCGCGCTCGGCTCGCTGGTCACCTATGTGCTGATCGAG
CGGTCCATGCGGTACAGCCGGCTCACACCGGCGGCGCTGGCCGTCGTTACCGCCGCATTCACACTGGGTGTGCAGCCCACCGGCCTGATC
GCGGTGGCCGCGCTGGTGGCCGGCGGCCGCCCGATGCTGCGGATCTTGGTGCGCCGTCATCGCCTGGTCGGCACGTTGCCGTTGGTGTCG
CCGATGCTGGCCGCCGGCACCGTCATCCTGACCGTGGTGTTCGCCGACCAGACCCTGTCAACGGTGTTGGAAGCCACCAGGGTTCGCGCC
AAAATCGGGCCGAGCCAGGCGTGGTATACCGAGAACCTGCGTTACTACTACCTCATCCTGCCCACCGTCGACGGTTCGCTGTCGCGGCGC
TTCGGCTTTTTGATCACCGCGCTATGCCTGTTCACCGCGGTGTTCATCATGTTGCGGCGCAAGCGAATTCCCAGCGTGGCCCGCGGACCG
GCGTGGCGGCTGATGGGCGTCATCTTCGGCACCATGTTCTTCCTGATGTTCACGCCCACCAAGTGGGTGCACCACTTCGGGCTGTTCGCC
GCCGTAGGGGCGGCGATGGCCGCGCTGACGACGGTGTTGGTATCCCCATCGGTGCTGCGCTGGTCGCGCAACCGGATGGCGTTCCTGGCG
GCGTTATTCTTCCTGCTGGCGTTGTGTTGGGCCACCACCAACGGCTGGTGGTATGTCTCCAGCTACGGTGTGCCGTTCAACAGCGCGATG
CCGAAGATCGACGGGATCACAGTCAGCACAATCTTTTTCGCCCTGTTTGCGATCGCCGCCGGCTATGCGGCCTGGCTGCACTTCGCGCCC
CGCGGCGCCGGCGAAGGGCGGCTGATCCGCGCGCTGACGACAGCCCCGGTACCGATCGTGGCCGGTTTCATGGCGGCGGTGTTCGTCGCG
TCCATGGTGGCCGGGATCGTGCGACAGTACCCGACCTACTCCAACGGCTGGTCCAACGTGCGGGCGTTTGTCGGCGGCTGCGGACTGGCC
GACGACGTACTCGTCGAGCCTGATACCAATGCGGGTTTCATGAAGCCGCTGGACGGCGATTCGGGTTCTTGGGGCCCCTTGGGCCCGCTG
GGTGGAGTCAACCCGGTCGGCTTCACGCCCAACGGCGTACCGGAACACACGGTGGCCGAGGCGATCGTGATGAAACCCAACCAGCCCGGC
ACCGACTACGACTGGGATGCGCCGACCAAGCTGACGAGTCCTGGCATCAATGGTTCTACGGTGCCGCTGCCCTATGGGCTCGATCCCGCC
CGGGTACCGTTGGCAGGCACCTACACCACCGGCGCACAGCAACAGAGCACACTCGTCTCGGCGTGGTATCTCCTGCCTAAGCCGGACGAC
GGGCATCCGCTGGTCGTGGTGACCGCCGCGGGCAAGATCGCCGGCAACAGCGTGCTGCACGGGTACACCCCCGGGCAGACTGTGGTGCTC
GAATACGCCATGCCGGGACCCGGAGCGCTGGTACCCGCCGGGCGGATGGTGCCCGACGACCTATACGGAGAGCAGCCCAAGGCGTGGCGC
AACCTGCGCTTCGCCCGAGCAAAGATGCCCGCCGATGCCGTCGCGGTCCGGGTGGTGGCCGAGGATCTGTCGCTGACACCGGAGGACTGG
ATCGCGGTGACCCCGCCGCGGGTACCGGACCTGCGCTCACTGCAGGAATATGTGGGCTCGACGCAGCCGGTGCTGCTGGACTGGGCGGTC
GGTTTGGCCTTCCCGTGCCAGCAGCCGATGCTGCACGCCAATGGCATCGCCGAAATCCCGAAGTTCCGCATCACACCGGACTACTCGGCT
AAGAAGCTGGACACCGACACGTGGGAAGACGGCACTAACGGCGGCCTGCTCGGGATCACCGACCTGTTGCTGCGGGCCCACGTCATGGCC
ACCTACCTGTCCCGCGACTGGGCCCGCGATTGGGGTTCCCTGCGCAAGTTCGACACCCTGGTCGATGCCCCTCCCGCCCAGCTCGAGTTG
GGCACCGCGACCCGCAGCGGCCTGTGGTCACCGGGCAAGATCCGAATTGGTCCATAG