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 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

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
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

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 30337678G-241A P6L I41M S224P L356V G363D Q365H A394S L469F A516T I586V V624_P626dup P626_P628dup P627_P629dup P627dup P628_P629dup P631S +631:S -631:P +631:PPW T658A

ReSeqTB:

High ConfidenceG363D T658A V624_P626dup P627dup P626_P628dup +631:PPW
Moderate ConfidenceQ365H A516T
Minimal ConfidenceP627_P629dup I41M -631:P
Indeterminate ConfidenceL356V P6L S224P

>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