Mycobacterium tuberculosis embC mutant conferring resistance to ethambutol

Download Sequences
Accession ARO:3003327
Synonym(s)Rv3793
CARD Short NameMtub_embC_EMB
DefinitionPoint mutations in Mycobacterium tuberculosis embC that result in lower affinity between ethambutol and EmbC, resulting in resistance.
AMR Gene Familyethambutol resistant embC
Drug Classpolyamine antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification10 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic ethambutol [Antibiotic]
+ ethambutol resistant embC [AMR Gene Family]
Publications

Safi H, et al. 2013. Nat Genet 45(10): 1190-1197. Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-beta-D-arabinose biosynthetic and utilization pathway genes. (PMID 23995136)

Jadaun GP, et al. 2009. Int J Antimicrob Agents 33(5): 483-486. Role of embCAB gene mutations in ethambutol resistance in Mycobacterium tuberculosis isolates from India. (PMID 19112008)

Xu Y, et al. 2015. Biomed Res Int 2015:951706 Mutations Found in embCAB, embR, and ubiA Genes of Ethambutol-Sensitive and -Resistant Mycobacterium tuberculosis Clinical Isolates from China. (PMID 26417605)

Srivastava S, et al. 2009. Int. J. Med. Microbiol. 299(4):269-80 emb nucleotide polymorphisms and the role of embB306 mutations in Mycobacterium tuberculosis resistance to ethambutol. (PMID 19010731)

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)

Plinke C, et al. 2010. J. Antimicrob. Chemother. 65(7):1359-67 embCAB sequence variation among ethambutol-resistant Mycobacterium tuberculosis isolates without embB306 mutation. (PMID 20427375)

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)

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 embC 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).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
Mycobacterium tuberculosis31.76%0%28.67%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): 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).

MutationMutation typePubMedReSeqTBCRyPTICWHO
A244T,G288W,V303Gmultiple resistance variantsPMID:19010731no datano datano data
A247P,T270I,I297Tmultiple resistance variantsPMID:19010731no datano datano data
A247P,I297L,W326Rmultiple resistance variantsPMID:19010731no datano datano data
A247Psingle resistance variantPMID:16972132no datano datano data
L251Rsingle resistance variantPMID:19112008no datano datano data
L251R,A254G,T270Imultiple resistance variantsPMID:19010731no datano datano data
A254Gsingle resistance variantPMID:16972132no datano datano data
T270I,Y296H,G308D,G325Smultiple resistance variantsPMID:19010731no datano datano data
T270I,G288W,V303Gmultiple resistance variantsPMID:19010731no datano datano data
T270I,I297Tmultiple resistance variantsPMID:19010731no datano datano data
T270Isingle resistance variantPMID:19112008ReSeqTB-Noneno datano data
G272S,H285Y,M300R,A307Tmultiple resistance variantsPMID:19010731no datano datano data
H285Ysingle resistance variantPMID:19112008no datano datano data
V287F,T309Nmultiple resistance variantsPMID:19010731no datano datano data
V287F,Y309Nmultiple resistance variantsPMID:19010731no datano datano data
V287Fsingle resistance variantPMID:23995136no datano datano data
G288Wsingle resistance variantPMID:19010731no datano datano data
G288W,V303Gmultiple resistance variantsPMID:19010731no datano datano data
G288Vsingle resistance variantPMID:19010731no datano datano data
G288V,M310K,Y327Nmultiple resistance variantsPMID:19010731no datano datano data
Y296S,R302Gmultiple resistance variantsPMID:19010731no datano datano data
Y296Ssingle resistance variantPMID:19010731no datano datano data
Y296Hsingle resistance variantPMID:19010731no datano datano data
I297Lsingle resistance variantPMID:19010731no datano datano data
I297L,W326Rmultiple resistance variantsPMID:19010731no datano datano data
I297Tsingle resistance variantPMID:19010731no datano datano data
M300Rsingle resistance variantPMID:19010731no datano datano data
R302Gsingle resistance variantPMID:19010731no datano datano data
V303Gsingle resistance variantPMID:19010731no datano datano data
A307Tsingle resistance variantPMID:19010731no datano datano data
G308Dsingle resistance variantPMID:19010731no datano datano data
Y309Nsingle resistance variantPMID:19010731no datano datano data
M310Ksingle resistance variantPMID:19010731no datano datano data
G325Ssingle resistance variantPMID:19010731no datano datano data
W326Rsingle resistance variantPMID:19010731no datano datano data
Y327Nsingle resistance variantPMID:19010731no datano datano data
N394Dsingle resistance variantPMID:10639358ReSeqTB-Noneno datano data
P398Ssingle resistance variantPMID:23995136no datano datano data
Q491Rsingle resistance variantPMID:23995136no datano datano data
L502Psingle resistance variantPMID:23995136no datano datano data
R738Qsingle resistance variantPMID:10639358no datano datano data
V981Lsingle resistance variantPMID:20427375ReSeqTB-Noneno datano data
V987Gsingle resistance variantno dataReSeqTB-Moderateno datano data

>gb|NP_218310.1|+|Mycobacterium tuberculosis embC mutant conferring resistance to ethambutol [Mycobacterium tuberculosis H37Rv]
MATEAAPPRIAVRLPSTSVRDAGANYRIARYVAVVAGLLGAVLAIATPLLPVNQTTAQLN
WPQNGTFASVEAPLIGYVATDLNITVPCQAAAGLAGSQNTGKTVLLSTVPKQAPKAVDRG
LLLQRANDDLVLVVRNVPLVTAPLSQVLGPTCQRLTFTAHADRVAAEFVGLVQGPNAEHP
GAPLRGERSGYDFRPQIVGVFTDLAGPAPPGLSFSASVDTRYSSSPTPLKMAAMILGVAL
TGAALVALHILDTADGMRHRRFLPARWWSTGGLDTLVIAVLVWWHFVGANTSDDGYILTM
ARVSEHAGYMANYYRWFGTPEAPFGWYYDLLALWAHVSTASIWMRLPTLAMALTCWWVIS
REVIPRLGHAVKTSRAAAWTAAGMFLAVWLPLDNGLRPEPIIALGILLTWCSVERAVATS
RLLPVAIACIIGALTLFSGPTGIASIGALLVAIGPLRTILHRRSRRFGVLPLVAPILAAA
TVTAIPIFRDQTFAGEIQANLLKRAVGPSLKWFDEHIRYERLFMASPDGSIARRFAVLAL
VLALAVSVAMSLRKGRIPGTAAGPSRRIIGITIISFLAMMFTPTKWTHHFGVFAGLAGSL
GALAAVAVTGAAMRSRRNRTVFAAVVVFVLALSFASVNGWWYVSNFGVPWSNSFPKWRWS
LTTALLELTVLVLLLAAWFHFVANGDGRRTARPTRFRARLAGIVQSPLAIATWLLVLFEV
VSLTQAMISQYPAWSVGRSNLQALAGKTCGLAEDVLVELDPNAGMLAPVTAPLADALGAG
LSEAFTPNGIPADVTADPVMERPGDRSFLNDDGLITGSEPGTEGGTTAAPGINGSRARLP
YNLDPARTPVLGSWRAGVQVPAMLRSGWYRLPTNEQRDRAPLLVVTAAGRFDSREVRLQW
ATDEQAAAGHHGGSMEFADVGAAPAWRNLRAPLSAIPSTATQVRLVADDQDLAPQHWIAL
TPPRIPRVRTLQNVVGAADPVFLDWLVGLAFPCQRPFGHQYGVDETPKWRILPDRFGAEA
NSPVMDHNGGGPLGITELLMRATTVASYLKDDWFRDWGALQRLTPYYPDAQPADLNLGTV
TRSGLWSPAPLRRG


>gb|NC_000962.3|+|4239863-4243147|Mycobacterium tuberculosis embC mutant conferring resistance to ethambutol [Mycobacterium tuberculosis H37Rv]
ATGGCTACCGAAGCCGCCCCACCCCGTATCGCCGTCCGGCTACCATCTACCTCCGTGCGCGACGCGGGAGCAAACTACCGGATCGCCCGG
TACGTCGCTGTGGTGGCGGGTCTGCTAGGCGCTGTGCTGGCCATCGCCACCCCACTGCTGCCGGTCAACCAGACCACCGCGCAATTGAAC
TGGCCCCAAAACGGCACGTTCGCCAGTGTCGAGGCACCGCTGATTGGCTACGTGGCCACCGACTTGAACATCACCGTCCCCTGCCAGGCC
GCCGCCGGACTGGCCGGATCGCAGAACACCGGCAAGACGGTGTTGTTGTCAACGGTGCCCAAGCAGGCGCCTAAGGCCGTCGATCGCGGG
CTGCTGCTGCAACGGGCCAACGACGACCTGGTGCTTGTGGTGCGTAATGTCCCGTTGGTCACCGCCCCGCTGAGTCAGGTGCTCGGCCCG
ACCTGTCAGCGGTTGACATTCACCGCGCACGCCGATCGGGTCGCCGCCGAATTCGTCGGACTGGTGCAGGGACCCAATGCTGAGCACCCC
GGTGCACCGCTGCGCGGTGAGCGCAGCGGCTACGACTTCCGCCCGCAGATCGTCGGGGTGTTCACCGACCTGGCCGGGCCGGCGCCACCG
GGTCTGAGCTTCTCGGCGAGCGTGGATACCCGCTACAGCAGCAGCCCCACGCCGCTGAAGATGGCCGCCATGATCCTCGGGGTAGCGCTC
ACCGGCGCCGCCCTGGTGGCGCTGCACATCCTGGACACCGCCGACGGCATGCGGCACCGGCGGTTCCTGCCCGCGCGCTGGTGGTCGACC
GGCGGTCTGGACACCCTGGTTATCGCCGTGCTGGTGTGGTGGCATTTCGTCGGGGCCAACACCTCCGACGACGGCTACATCCTGACCATG
GCCCGGGTGTCCGAGCATGCGGGCTATATGGCCAACTACTACCGCTGGTTCGGCACACCCGAGGCGCCTTTCGGCTGGTACTACGACCTG
CTGGCGCTGTGGGCTCATGTCAGCACGGCCAGTATCTGGATGCGCCTACCCACCCTGGCGATGGCGCTCACCTGCTGGTGGGTAATCAGC
CGTGAGGTCATTCCCCGGCTGGGGCACGCCGTCAAGACGAGCCGGGCAGCGGCGTGGACGGCGGCGGGCATGTTTCTGGCTGTCTGGCTG
CCGCTGGACAACGGCCTTCGGCCCGAGCCGATCATCGCCCTGGGCATCCTGCTGACCTGGTGCTCGGTGGAGCGGGCGGTGGCCACCAGC
CGGCTGCTGCCGGTGGCAATCGCCTGCATCATCGGTGCCTTGACCCTGTTCTCCGGGCCGACGGGCATCGCCTCGATCGGTGCGCTGCTG
GTCGCGATCGGGCCGCTACGGACCATCCTGCACCGGCGTTCCAGGCGGTTCGGCGTGCTACCACTGGTGGCGCCGATCCTGGCCGCGGCC
ACCGTCACCGCGATCCCGATCTTTCGTGATCAGACCTTCGCGGGCGAGATCCAGGCCAACCTCCTCAAGCGTGCCGTAGGGCCCAGCCTG
AAGTGGTTCGACGAACACATCCGCTACGAGCGGCTGTTCATGGCCAGCCCCGACGGCTCGATCGCCCGCCGCTTCGCCGTGCTGGCCTTG
GTGCTGGCGCTCGCGGTATCGGTGGCAATGTCGTTACGTAAGGGCCGCATTCCAGGTACCGCTGCTGGACCGAGCCGCCGCATCATCGGC
ATCACGATCATTTCCTTCCTCGCGATGATGTTCACCCCGACAAAGTGGACCCATCACTTCGGGGTGTTCGCGGGGTTGGCCGGGTCGCTG
GGGGCGCTTGCCGCGGTCGCGGTGACGGGCGCTGCGATGCGCTCGCGGCGGAACCGGACCGTGTTCGCCGCCGTGGTGGTCTTCGTGTTG
GCCCTGTCGTTCGCCAGTGTCAACGGCTGGTGGTACGTGTCCAACTTCGGTGTGCCATGGTCGAACTCGTTTCCGAAGTGGCGATGGTCG
CTTACCACCGCACTCCTCGAGCTGACGGTGCTGGTGCTGCTGCTAGCGGCATGGTTCCACTTCGTCGCCAACGGTGACGGGCGCCGAACA
GCCAGGCCAACCCGGTTTAGGGCACGACTAGCCGGAATTGTCCAGTCCCCGTTGGCAATTGCCACGTGGTTGCTGGTGCTTTTCGAGGTG
GTATCGCTGACCCAGGCGATGATTTCCCAGTACCCGGCGTGGTCGGTTGGCCGGTCTAACCTACAGGCTTTGGCCGGCAAGACCTGCGGG
CTGGCCGAAGACGTGCTGGTGGAGCTGGATCCCAACGCAGGCATGCTGGCGCCGGTGACCGCGCCGTTGGCCGACGCCCTGGGAGCCGGC
CTGTCTGAAGCCTTCACACCCAACGGCATTCCCGCCGACGTCACCGCCGACCCGGTGATGGAACGTCCAGGGGATCGCAGTTTCCTCAAC
GACGACGGGCTGATCACCGGCAGCGAACCCGGCACCGAAGGGGGCACCACGGCCGCACCGGGAATCAACGGCTCCCGCGCCCGGCTGCCC
TACAACCTGGACCCGGCCCGTACACCGGTGCTGGGCAGCTGGCGAGCCGGCGTGCAGGTGCCCGCCATGCTGCGGTCGGGCTGGTACCGG
CTGCCCACCAACGAGCAGCGGGACAGGGCGCCGCTGCTGGTGGTGACGGCGGCCGGGCGATTCGACTCCCGCGAGGTCCGGTTGCAGTGG
GCCACCGACGAGCAAGCGGCCGCCGGACACCACGGTGGGTCGATGGAATTCGCCGACGTCGGTGCCGCGCCGGCCTGGCGCAACCTGCGC
GCACCACTGTCCGCCATCCCGAGCACCGCCACCCAGGTCCGGTTGGTCGCCGACGACCAGGATCTGGCGCCGCAGCACTGGATCGCCCTC
ACACCACCGCGGATTCCGCGGGTGCGCACGCTGCAGAACGTGGTGGGCGCAGCGGATCCGGTGTTCCTGGACTGGCTGGTGGGGCTGGCA
TTCCCCTGCCAACGCCCGTTCGGCCACCAATACGGCGTCGACGAGACACCCAAGTGGCGGATCCTGCCGGACCGGTTCGGCGCCGAAGCC
AACTCACCGGTGATGGATCACAATGGCGGTGGCCCGCTGGGCATCACCGAGCTGCTGATGCGCGCAACCACGGTGGCCAGCTACCTCAAA
GACGACTGGTTTAGGGACTGGGGCGCGTTACAGCGGTTGACGCCTTACTACCCCGACGCCCAGCCCGCTGATCTGAACCTAGGAACGGTG
ACTCGCAGCGGGCTGTGGAGTCCGGCGCCGTTGCGCCGCGGCTAG

Curator Acknowledgements
Curator Description Most Recent Edit