Mycobacterium tuberculosis Rv0678 with mutation conferring resistance to bedaquiline

Accession ARO:3007674
Synonym(s)Rv0678
CARD Short NameMtub_Rv0678_BDQ
DefinitionRv0678 encodes a transcription factor which negatively regulates the expression of the mmpS5/L5 efflux pump. Loss-of-function mutations in rv0678 are a common mechanism of resistance.
AMR Gene Familybedaquiline resistant Rv0678
Drug Classdiarylquinoline antibiotic
Resistance Mechanismantibiotic target alteration
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic bedaquiline [Antibiotic]
+ bedaquiline resistant Rv0678 [AMR Gene Family]
Publications

Otum CC, et al. 2023. Sci Rep 13(1):9212 Site-directed mutagenesis of Mycobacterium tuberculosis and functional validation to investigate potential bedaquiline resistance-causing mutations. (PMID 37280265)

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)

Resistomes

Prevalence of Mycobacterium tuberculosis Rv0678 with mutation conferring resistance to bedaquiline 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): 300

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
Q22Ternonsense mutationno datano datano dataWHO-R
L32Ssingle resistance variantno datano datano dataWHO-R
T33Asingle resistance variantPMID:37280265no datano datano data
A36Vsingle resistance variantno datano datano dataWHO-R
R38Ternonsense mutationno datano datano dataWHO-R
W42Ternonsense mutationno datano datano dataWHO-R
C46Rsingle resistance variantno datano datano dataWHO-R
S53Ternonsense mutationno datano datano dataWHO-R
I67Ssingle resistance variantno datano datano dataWHO-R
N70Dsingle resistance variantno datano datano dataWHO-R
Q76Ternonsense mutationno datano datano dataWHO-R
Y92Ternonsense mutationno datano datano dataWHO-R
E113Ternonsense mutationno datano datano dataWHO-R
Q115Ternonsense mutationno datano datano dataWHO-R
L117Rsingle resistance variantno datano datano dataWHO-R
G121Rsingle resistance variantno datano datano dataWHO-R
R132Ternonsense mutationno datano datano dataWHO-R
R134Ternonsense mutationno datano datano dataWHO-R
E138Ternonsense mutationno datano datano dataWHO-R
Y145Ternonsense mutationno datano datano dataWHO-R
M146Tsingle resistance variantno datano datano dataWHO-R
E147Ternonsense mutationno datano datano dataWHO-R
R156Ternonsense mutationno datano datano dataWHO-R
Y157Ternonsense mutationno datano datano dataWHO-R

>gb|NP_215192.1|+|Mycobacterium tuberculosis Rv0678 with mutation conferring resistance to bedaquiline [Mycobacterium tuberculosis H37Rv]
MSVNDGVDQMGAEPDIMEFVEQMGGYFESRSLTRLAGRLLGWLLVCDPERQSSEELATAL
AASSGGISTNARMLIQFGFIERLAVAGDRRTYFRLRPNAFAAGERERIRAMAELQDLADV
GLRALGDAPPQRSRRLREMRDLLAYMENVVSDALGRYSQRTGEDD



>gb|NC_000962.3|+|778990-779487|Mycobacterium tuberculosis Rv0678 with mutation conferring resistance to bedaquiline [Mycobacterium tuberculosis H37Rv]
GTGAGCGTCAACGACGGGGTCGATCAGATGGGCGCCGAGCCCGACATCATGGAATTCGTCGAACAGATGGGCGGCTATTTCGAGTCCAGG
AGTTTGACTCGGTTGGCGGGTCGATTGTTGGGCTGGCTGCTGGTGTGTGATCCCGAGCGGCAGTCCTCGGAGGAACTGGCGACGGCGCTG
GCGGCCAGCAGCGGGGGGATCAGCACCAATGCCCGGATGCTGATCCAATTTGGGTTCATTGAGCGGCTCGCGGTCGCCGGGGATCGGCGC
ACCTATTTCCGGTTGCGGCCCAACGCTTTCGCGGCTGGCGAGCGTGAACGCATCCGGGCAATGGCCGAACTGCAGGACCTGGCTGACGTG
GGGCTGAGGGCGCTGGGCGACGCCCCGCCGCAGCGAAGCCGACGGCTGCGGGAGATGCGGGATCTGTTGGCATATATGGAGAACGTCGTC
TCCGACGCCCTGGGGCGATACAGCCAGCGAACCGGAGAGGACGACTGA

Curator Acknowledgements
Curator Description Most Recent Edit