Mycobacterium tuberculosis ponA1 mutations confer resistance to rifabutin

Accession ARO:3004960
Synonym(s)Rv0050
CARD Short NameMtub_ponA1_RFB
DefinitionMutations in ponA1 that contribute to or confer resistance to rifabutin antibiotic.
AMR Gene Familyrifamycin resistant ponA1
Drug Classrifamycin antibiotic
Resistance Mechanismantibiotic target alteration
Classification9 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic rifampin [Antibiotic]
+ confers_resistance_to_antibiotic rifabutin [Antibiotic]
+ rifamycin resistant ponA1 [AMR Gene Family]
Publications

Farhat MR, et al. 2013. Nat Genet 45(10):1183-9 Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. (PMID 23995135)

Trauner A, et al. 2014. Drugs 74(10):1063-72 Evolution of drug resistance in tuberculosis: recent progress and implications for diagnosis and therapy. (PMID 24962424)

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 ponA1 mutations confer resistance to rifabutin 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): 1275

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
I41Msingle resistance variantno dataReSeqTB-Minimalno datano data
G363Dsingle resistance variantno dataReSeqTB-Highno datano data
Q365Hsingle resistance variantno dataReSeqTB-Moderateno datano data
A516Tsingle resistance variantno dataReSeqTB-Moderateno datano data
V624_P626dupinsertion mutation from peptide sequenceno dataReSeqTB-Highno datano data
P626_P628dupinsertion mutation from peptide sequenceno dataReSeqTB-Highno datano data
P627dupinsertion mutation from peptide sequenceno dataReSeqTB-Highno datano data
P627_P629dupinsertion mutation from peptide sequenceno dataReSeqTB-Minimalno datano data
-P631deletion mutation from peptide sequenceno dataReSeqTB-Minimalno datano data
+PPW631insertion mutation from peptide sequenceno dataReSeqTB-Highno datano data
T658Asingle resistance variantno dataReSeqTB-Highno datano data

>gb|YP_177687.1|+|Mycobacterium tuberculosis ponA1 mutations confer resistance to rifabutin [Mycobacterium tuberculosis H37Rv]
MVILLPMVTFTMAYLIVDVPKPGDIRTNQVSTILASDGSEIAKIVPPEGNRVDVNLSQVP
MHVRQAVIAAEDRNFYSNPGFSFTGFARAVKNNLFGGDLQGGSTITQQYVKNALVGSAQH
GWSGLMRKAKELVIATKMSGEWSKDDVLQAYLNIIYFGRGAYGISAASKAYFDKPVEQLT
VAEGALLAALIRRPSTLDPAVDPEGAHARWNWVLDGMVETKALSPNDRAAQVFPETVPPD
LARAENQTKGPNGLIERQVTRELLELFNIDEQTLNTQGLVVTTTIDPQAQRAAEKAVAKY
LDGQDPDMRAAVVSIDPHNGAVRAYYGGDNANGFDFAQAGLQTGSSFKVFALVAALEQGI
GLGYQVDSSPLTVDGIKITNVEGEGCGTCNIAEALKMSLNTSYYRLMLKLNGGPQAVADA
AHQAGIASSFPGVAHTLSEDGKGGPPNNGIVLGQYQTRVIDMASAYATLAASGIYHPPHF
VQKVVSANGQVLFDASTADNTGDQRIPKAVADNVTAAMEPIAGYSRGHNLAGGRDSAAKT
GTTQFGDTTANKDAWMVGYTPSLSTAVWVGTVKGDEPLVTASGAAIYGSGLPSDIWKATM
DGALKGTSNETFPKPTEVGGYAGVPPPPPPPEVPPSETVIQPTVEIAPGITIPIGPPTTI
TLAPPPPAPPAATPTPPP



>gb|NC_000962.3|+|53663-55699|Mycobacterium tuberculosis ponA1 mutations confer resistance to rifabutin [Mycobacterium tuberculosis H37Rv]
GTGGTGATCCTGTTGCCGATGGTCACCTTCACGATGGCCTACCTGATCGTCGACGTTCCCAAGCCAGGTGACATCCGTACCAACCAGGTC
TCCACGATCCTTGCCAGCGACGGCTCGGAAATCGCCAAAATTGTTCCGCCCGAAGGTAATCGGGTCGACGTCAACCTCAGCCAGGTGCCG
ATGCATGTGCGCCAGGCGGTGATTGCGGCCGAAGACCGCAATTTCTATTCGAATCCGGGATTCTCGTTCACCGGCTTCGCGCGGGCAGTC
AAGAACAACCTGTTCGGCGGCGATCTGCAGGGCGGATCGACGATTACCCAGCAGTACGTCAAGAACGCGCTGGTCGGTTCCGCACAGCAC
GGGTGGAGCGGTCTGATGCGCAAGGCGAAAGAATTGGTCATCGCGACGAAGATGTCGGGGGAGTGGTCTAAAGACGATGTGCTGCAGGCG
TATCTGAACATCATCTACTTCGGCCGGGGCGCCTACGGCATTTCGGCGGCGTCCAAGGCTTATTTCGACAAGCCCGTCGAGCAGCTGACC
GTTGCCGAAGGGGCGTTGTTGGCAGCGCTGATTCGGCGGCCTTCGACGCTGGACCCGGCGGTCGACCCCGAAGGGGCCCATGCCCGCTGG
AATTGGGTACTCGACGGCATGGTGGAAACCAAGGCTCTCTCGCCGAATGACCGTGCGGCGCAGGTGTTTCCCGAGACAGTGCCGCCCGAT
CTGGCCCGGGCAGAGAATCAGACCAAAGGACCCAACGGGCTGATCGAGCGGCAGGTGACAAGGGAGTTGCTCGAGCTGTTCAACATCGAC
GAGCAGACCCTCAACACCCAGGGGCTGGTGGTCACCACCACGATTGATCCGCAGGCCCAACGGGCGGCGGAGAAGGCGGTTGCGAAATAC
CTGGACGGGCAGGACCCCGACATGCGTGCCGCCGTGGTTTCCATCGACCCGCACAACGGGGCGGTGCGTGCGTACTACGGTGGCGACAAT
GCCAATGGCTTTGACTTCGCTCAAGCGGGATTGCAGACTGGATCGTCGTTTAAGGTGTTTGCTCTGGTGGCCGCCCTTGAGCAGGGGATC
GGCCTGGGCTACCAGGTAGACAGCTCTCCGTTGACGGTCGACGGCATCAAGATCACCAACGTCGAGGGCGAGGGTTGCGGGACGTGCAAC
ATCGCCGAGGCGCTCAAAATGTCGCTGAACACCTCCTACTACCGGCTGATGCTCAAGCTCAACGGCGGCCCACAGGCTGTGGCCGATGCC
GCGCACCAAGCCGGCATTGCCTCCAGCTTCCCGGGCGTTGCGCACACGCTGTCCGAAGATGGCAAGGGTGGACCGCCCAACAACGGGATC
GTGTTGGGCCAGTACCAAACCCGGGTGATCGACATGGCATCGGCGTATGCCACGTTGGCCGCGTCCGGTATCTACCACCCGCCGCATTTC
GTACAGAAGGTGGTCAGTGCCAACGGCCAGGTCCTCTTCGACGCCAGCACCGCGGACAACACCGGCGATCAGCGCATCCCCAAGGCGGTA
GCCGACAACGTGACTGCGGCGATGGAGCCGATCGCAGGTTATTCGCGTGGCCACAACCTAGCGGGTGGGCGGGATTCGGCGGCCAAGACC
GGCACTACGCAATTTGGTGACACCACCGCGAACAAAGACGCCTGGATGGTCGGGTACACGCCGTCGTTGTCTACGGCTGTGTGGGTGGGC
ACCGTCAAGGGTGACGAGCCACTGGTAACCGCTTCGGGTGCAGCGATTTACGGCTCGGGCCTGCCGTCGGACATCTGGAAGGCAACCATG
GACGGCGCCTTGAAGGGCACGTCGAACGAGACTTTCCCCAAACCGACCGAGGTCGGTGGTTATGCCGGTGTGCCGCCGCCGCCGCCGCCG
CCGGAGGTACCACCTTCGGAGACCGTCATCCAGCCCACGGTCGAAATTGCGCCGGGGATTACCATCCCGATCGGTCCCCCGACCACCATT
ACCCTGGCGCCACCGCCCCCGGCCCCGCCCGCTGCGACTCCCACGCCGCCGCCGTGA

Curator Acknowledgements
Curator Description Most Recent Edit