Mycobacterium tuberculosis tlyA mutations conferring resistance to aminoglycosides

Accession ARO:3003445
Synonym(s)Rv1694
CARD Short NameMtub_tlyA_AMG
DefinitionSpecific mutations that arise in Mycobacterium tuberculosis tlyA resulting in aminoglycosides resistance.
AMR Gene FamilyAntibiotic resistant tlyA
Drug Classaminoglycoside antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification12 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic streptomycin [Antibiotic]
+ Antibiotic resistant tlyA [AMR Gene Family]
+ confers_resistance_to_antibiotic capreomycin [Antibiotic]
Publications

Maus CE, et al. 2005. Antimicrob Agents Chemother 49(2): 571-577. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. (PMID 15673735)

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 tlyA mutations conferring resistance to aminoglycosides 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 tuberculosis0.2%0%0.03%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): 450

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
R3Ternonsense mutationPMID:15673735no datano datano data
R14Wsingle resistance variantPMID:15673735no datano datano data
R18Ternonsense mutationPMID:15673735no datano datano data
Q22Ternonsense mutationPMID:15673735no datano datano data
-nt23:adeletion mutation from nucleotide sequencePMID:15673735no datano datano data
-nt26:cdeletion mutation from nucleotide sequencePMID:15673735no datano datano data
K31fsframeshift mutationno dataReSeqTB-Highno datano data
A67Esingle resistance variantPMID:15673735no datano datano data
K69Esingle resistance variantPMID:15673735no datano datano data
A91Esingle resistance variantPMID:15673735no datano datano data
L118Psingle resistance variantPMID:15673735no datano datano data
V128Esingle resistance variantPMID:15673735no datano datano data
L150Psingle resistance variantPMID:15673735no datano datano data
P183Lsingle resistance variantPMID:15673735no datano datano data
Q184Ternonsense mutationPMID:15673735no datano datano data
F185Lsingle resistance variantPMID:15673735no datano datano data
N236Ksingle resistance variantPMID:15673735no datano datano data
E238Ksingle resistance variantPMID:15673735no datano datano data
-nt310:gdeletion mutation from nucleotide sequencePMID:15673735no datano datano data
+nt397:cinsertion mutation from nucleotide sequencePMID:15673735no datano datano data
-nt400:adeletion mutation from nucleotide sequencePMID:15673735no datano datano data
-nt477:gdeletion mutation from nucleotide sequencePMID:15673735no datano datano data
-nt586:gdeletion mutation from nucleotide sequencePMID:15673735no datano datano data
-nt653:tdeletion mutation from nucleotide sequencePMID:15673735no datano datano data
-nt673:gtdeletion mutation from nucleotide sequencePMID:15673735no datano datano data
-nt758:gdeletion mutation from nucleotide sequencePMID:15673735no datano datano data

>gb|NP_216210.1|+|Mycobacterium tuberculosis tlyA mutations conferring resistance to aminoglycosides [Mycobacterium tuberculosis H37Rv]
MARRARVDAELVRRGLARSRQQAAELIGAGKVRIDGLPAVKPATAVSDTTALTVVTDSER
AWVSRGAHKLVGALEAFAIAVAGRRCLDAGASTGGFTEVLLDRGAAHVVAADVGYGQLAW
SLRNDPRVVVLERTNARGLTPEAIGGRVDLVVADLSFISLATVLPALVGCASRDADIVPL
VKPQFEVGKGQVGPGGVVHDPQLRARSVLAVARRAQELGWHSVGVKASPLPGPSGNVEYF
LWLRTQTDRALSAKGLEDAVHRAISEGP



>gb|NC_000962.3|+|1917940-1918746|Mycobacterium tuberculosis tlyA mutations conferring resistance to aminoglycosides [Mycobacterium tuberculosis H37Rv]
GTGGCACGACGTGCCCGCGTTGACGCCGAGCTAGTCCGGCGGGGCCTGGCGCGATCACGTCAACAGGCCGCGGAGTTGATCGGCGCCGGC
AAGGTGCGCATCGACGGGCTGCCGGCGGTCAAGCCGGCCACCGCCGTGTCCGACACCACCGCGCTGACCGTGGTGACCGACAGTGAACGC
GCCTGGGTATCGCGCGGAGCGCACAAACTAGTCGGTGCGCTGGAGGCGTTCGCGATCGCGGTGGCGGGCCGGCGCTGTCTGGACGCGGGC
GCATCGACCGGTGGGTTCACCGAAGTACTGCTGGACCGTGGTGCCGCCCACGTGGTGGCCGCCGATGTCGGATACGGCCAGCTGGCGTGG
TCGCTGCGCAACGATCCTCGGGTGGTGGTCCTCGAGCGGACCAACGCACGTGGCCTCACACCGGAGGCGATCGGCGGTCGCGTCGACCTG
GTAGTGGCCGACCTGTCGTTCATCTCGTTGGCTACCGTGTTGCCCGCGCTGGTTGGATGCGCTTCGCGCGACGCCGATATCGTTCCACTG
GTGAAGCCGCAGTTTGAGGTGGGGAAAGGTCAGGTCGGCCCCGGTGGGGTGGTCCATGACCCGCAGTTGCGTGCGCGGTCGGTGCTCGCG
GTCGCGCGGCGGGCACAGGAGCTGGGCTGGCACAGCGTCGGCGTCAAGGCCAGCCCGCTGCCGGGCCCATCGGGCAATGTCGAGTACTTC
CTGTGGTTGCGCACGCAGACCGACCGGGCATTGTCGGCCAAGGGATTGGAGGATGCGGTGCACCGTGCGATTAGCGAGGGCCCGTAG

Curator Acknowledgements
Curator Description Most Recent Edit