Mycobacterium tuberculosis ppsD mutations confer resistance to pyrazinamide

Accession ARO:3004976
Synonym(s)Rv2934
CARD Short NameMtub_ppsD_PZA
DefinitionMutations in ppsD can contribute to or confer resistance to pyrazinamide.
AMR Gene Familyantibiotic resistant polyketide synthase genes
Drug Classpyrazine antibiotic
Resistance Mechanismantibiotic target alteration
Classification10 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic pyrazinamide [Antibiotic]
+ pyrazinamide resistant ppsD
Publications

Kavvas ES, et al. 2018. Nat Commun 9(1):4306 Machine learning and structural analysis of Mycobacterium tuberculosis pan-genome identifies genetic signatures of antibiotic resistance. (PMID 30333483)

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 ppsD mutations confer resistance to pyrazinamide 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): 3575

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 30337678M127I V295M A437P P563H A1248T V1266G I1508L V1522A A1639V E1823A

ReSeqTB:

High ConfidenceP563H M127I E1823A V295M
Moderate ConfidenceI1508L
Minimal ConfidenceA437P A1248T V1522A
Indeterminate ConfidenceA1639V

>gb|NP_217450.1|+|Mycobacterium tuberculosis ppsD mutations confer resistance to pyrazinamide [Mycobacterium tuberculosis H37Rv]
MTSLAERAAQLSPNARAALARELVRAGTTFPTDICEPVAVVGIGCRFPGNVTGPESFWQL
LADGVDTIEQVPPDRWDADAFYDPDPSASGRMTTKWGGFVSDVDAFDADFFGITPREAVA
MDPQHRMLLEVAWEALEHAGIPPDSLSGTRTGVMMGLSSWDYTIVNIERRADIDAYLSTG
TPHCAAVGRIAYLLGLRGPAVAVDTACSSSLVAIHLACQSLRLRETDVALAGGVQLTLSP
FTAIALSKWSALSPTGRCNSFDANADGFVRGEGCGVVVLKRLADAVRDQDRVLAVVRGSA
TNSDGRSNGMTAPNALAQRDVITSALKLADVTPDSVNYVETHGTGTVLGDPIEFESLAAT
YGLGKGQGESPCALGSVKTNIGHLEAAAGVAGFIKAVLAVQRGHIPRNLHFTRWNPAIDA
SATRLFVPTESAPWPAAAGPRRAAVSSFGLSGTNAHVVVEQAPDTAVAAAGGMPYVSALN
VSGKTAARVASAAAVLADWMSGPGAAAPLADVAHTLNRHRARHAKFATVIARDRAEAIAG
LRALAAGQPRVGVVDCDQHAGGPGRVFVYSGQGSQWASMGQQLLANEPAFAKAVAELDPI
FVDQVGFSLQQTLIDGDEVVGIDRIQPVLVGMQLALTELWRSYGVIPDAVIGHSMGEVSA
AVVAGALTPEQGLRVITTRSRLMARLSGQGAMALLELDADAAEALIAGYPQVTLAVHASP
RQTVIAGPPEQVDTVIAAVATQNRLARRVEVDVASHHPIIDPILPELRSALADLTPQPPS
IPIISTTYESAQPVADADYWSANLRNPVRFHQAVTAAGVDHNTFIEISPHPVLTHALTDT
LDPDGSHTVMSTMNRELDQTLYFHAQLAAVGVAASEHTTGRLVDLPPTPWHHQRFWVTDR
SAMSELAATHPLLGAHIEMPRNGDHVWQTDVGTEVCPWLADHKVFGQPIMPAAGFAEIAL
AAASEALGTAADAVAPNIVINQFEVEQMLPLDGHTPLTTQLIRGGDSQIRVEIYSRTRGG
EFCRHATAKVEQSPRECAHAHPEAQGPATGTTVSPADFYALLRQTGQHHGPAFAALSRIV
RLADGSAETEISIPDEAPRHPGYRLHPVVLDAALQSVGAAIPDGEIAGSAEASYLPVSFE
TIRVYRDIGRHVRCRAHLTNLDGGTGKMGRIVLINDAGHIAAEVDGIYLRRVERRAVPLP
LEQKIFDAEWTESPIAAVPAPEPAAETTRGSWLVLADATVDAPGKAQAKSMADDFVQQWR
SPMRRVHTADIHDESAVLAAFAETAGDPEHPPVGVVVFVGGASSRLDDELAAARDTVWSI
TTVVRAVVGTWHGRSPRLWLVTGGGLSVADDEPGTPAAASLKGLVRVLAFEHPDMRTTLV
DLDITQDPLTALSAELRNAGSGSRHDDVIAWRGERRFVERLSRATIDVSKGHPVVRQGAS
YVVTGGLGGLGLVVARWLVDRGAGRVVLGGRSDPTDEQCNVLAELQTRAEIVVVRGDVAS
PGVAEKLIETARQSGGQLRGVVHAAAVIEDSLVFSMSRDNLERVWAPKATGALRMHEATA
DCELDWWLGFSSAASLLGSPGQAAYACASAWLDALVGWRRASGLPAAVINWGPWSEVGVA
QALVGSVLDTISVAEGIEALDSLLAADRIRTGVARLRADRALVAFPEIRSISYFTQVVEE
LDSAGDLGDWGGPDALADLDPGEARRAVTERMCARIAAVMGYTDQSTVEPAVPLDKPLTE
LGLDSLMAVRIRNGARADFGVEPPVALILQGASLHDLTADLMRQLGLNDPDPALNNADTI
RDRARQRAAARHGAAMRRRPKPEVQGG



>gb|NC_000962.3|+|3262248-3267731|Mycobacterium tuberculosis ppsD mutations confer resistance to pyrazinamide [Mycobacterium tuberculosis H37Rv]
ATGACAAGTCTGGCGGAGCGCGCGGCGCAACTGTCGCCGAACGCGCGAGCGGCCCTGGCGCGCGAGCTCGTCCGTGCGGGTACGACCTTC
CCGACCGACATCTGCGAGCCGGTGGCGGTGGTGGGCATCGGCTGTCGCTTTCCGGGGAATGTGACTGGGCCAGAGAGCTTTTGGCAGCTA
CTGGCCGACGGTGTGGACACAATCGAGCAGGTGCCGCCTGATCGGTGGGATGCGGACGCGTTCTACGATCCCGATCCTTCGGCGTCGGGT
CGGATGACGACGAAATGGGGTGGTTTCGTTTCCGATGTCGACGCGTTCGACGCCGACTTTTTCGGAATCACTCCTCGGGAAGCCGTGGCG
ATGGACCCGCAGCATCGGATGCTGCTCGAGGTTGCCTGGGAAGCGTTGGAGCACGCGGGTATTCCGCCGGATTCCTTGAGCGGCACTCGA
ACCGGCGTGATGATGGGTCTGTCGTCGTGGGACTACACGATCGTCAATATCGAGCGCAGAGCCGACATCGACGCGTACCTGAGCACCGGA
ACCCCGCACTGTGCCGCGGTGGGGCGGATCGCGTATCTGTTGGGATTGCGTGGTCCGGCCGTCGCCGTAGATACCGCTTGTTCGTCGTCG
CTGGTGGCAATTCACTTGGCGTGTCAGAGCCTTCGCCTGCGTGAAACCGACGTGGCATTGGCGGGCGGGGTGCAGCTCACCTTGTCACCG
TTCACCGCCATCGCGCTGTCCAAGTGGTCGGCGCTGTCACCGACCGGCCGATGCAACAGCTTCGACGCCAACGCGGATGGATTCGTGCGC
GGCGAGGGCTGCGGCGTGGTGGTGCTCAAGCGGTTGGCCGACGCGGTGCGCGACCAGGACCGGGTGCTTGCGGTGGTCCGCGGTTCGGCA
ACTAACTCCGATGGTCGGTCCAACGGCATGACCGCACCGAACGCGCTGGCGCAGCGTGACGTGATCACATCCGCCCTCAAGCTTGCGGAT
GTTACCCCTGACAGCGTGAACTATGTCGAAACACACGGCACCGGAACGGTGTTGGGGGACCCCATCGAGTTCGAGTCGCTGGCGGCCACT
TATGGCCTGGGTAAAGGCCAGGGCGAGAGCCCGTGCGCATTGGGGTCGGTCAAGACCAACATCGGCCACCTGGAGGCGGCCGCCGGTGTG
GCTGGATTCATCAAGGCGGTGCTGGCGGTGCAACGTGGGCACATTCCCCGCAACTTGCACTTCACCCGGTGGAACCCGGCCATCGACGCG
TCGGCGACGCGGCTGTTCGTGCCGACCGAAAGCGCCCCGTGGCCGGCGGCTGCCGGTCCACGCAGGGCTGCGGTGTCATCGTTCGGCCTC
AGCGGGACCAACGCGCACGTGGTGGTCGAGCAGGCACCCGACACCGCAGTAGCCGCAGCCGGCGGCATGCCGTATGTTTCGGCGCTGAAC
GTCTCCGGCAAGACGGCCGCGCGGGTGGCGTCGGCGGCGGCGGTGCTGGCCGACTGGATGTCGGGGCCGGGCGCGGCGGCACCACTGGCC
GACGTGGCACACACGTTGAACCGGCACCGGGCCCGGCACGCCAAGTTCGCCACCGTCATCGCGCGTGACCGCGCCGAGGCGATCGCGGGG
TTGCGAGCGCTGGCGGCCGGACAACCACGCGTTGGGGTGGTGGATTGCGACCAGCATGCCGGTGGGCCTGGCCGGGTTTTTGTGTATTCG
GGTCAGGGCTCGCAGTGGGCGTCGATGGGCCAGCAGTTGCTGGCCAACGAACCGGCGTTCGCCAAGGCGGTAGCCGAGCTGGATCCGATA
TTCGTTGACCAGGTTGGCTTTTCGCTGCAGCAAACGCTTATCGACGGCGACGAGGTGGTGGGCATCGACCGCATCCAGCCGGTGCTGGTC
GGGATGCAGTTGGCGCTGACCGAGTTATGGCGGTCCTATGGGGTGATTCCAGATGCCGTGATCGGGCACTCGATGGGTGAGGTGTCGGCG
GCAGTGGTGGCCGGCGCGTTGACGCCCGAGCAGGGCTTGCGGGTCATCACCACCCGGTCGCGGTTGATGGCGCGGCTGTCGGGGCAGGGA
GCGATGGCGCTGCTCGAGCTGGATGCCGACGCCGCCGAGGCGCTGATTGCCGGCTATCCGCAGGTGACGCTGGCGGTGCATGCGTCACCG
CGCCAGACGGTGATCGCCGGGCCGCCCGAGCAGGTGGACACGGTGATCGCGGCGGTAGCGACGCAAAACCGGTTGGCGCGCCGCGTCGAA
GTCGACGTGGCCTCCCATCACCCGATCATCGATCCCATACTGCCCGAGTTGCGAAGCGCGTTAGCGGATTTGACTCCGCAGCCGCCGAGC
ATCCCGATCATTTCCACTACGTACGAAAGCGCGCAGCCGGTGGCGGATGCCGACTATTGGTCGGCCAACCTGCGCAACCCGGTGCGATTC
CACCAGGCCGTCACCGCCGCCGGTGTCGACCACAACACCTTCATCGAAATCAGCCCTCACCCCGTGCTCACGCACGCACTCACCGACACC
CTGGATCCGGACGGCAGCCATACAGTCATGTCGACGATGAACCGCGAACTGGACCAGACGCTGTATTTCCACGCCCAACTCGCCGCGGTC
GGTGTGGCTGCGTCCGAGCACACCACCGGTCGCCTTGTCGACCTGCCCCCCACACCGTGGCACCATCAGCGATTCTGGGTCACGGATCGT
TCGGCGATGTCCGAGCTGGCCGCGACCCACCCGCTCCTGGGCGCGCACATCGAGATGCCGCGCAACGGAGACCATGTCTGGCAGACCGAT
GTCGGCACCGAGGTCTGTCCCTGGTTGGCAGACCACAAGGTGTTCGGTCAACCCATCATGCCGGCCGCGGGGTTCGCCGAGATCGCCTTG
GCGGCGGCCAGCGAAGCCCTCGGCACAGCCGCCGACGCCGTCGCACCCAACATCGTGATCAACCAGTTCGAGGTGGAGCAGATGCTGCCC
CTCGACGGCCACACGCCGCTAACGACGCAGTTAATTCGCGGCGGGGACAGCCAGATTCGGGTCGAGATCTATTCCCGCACGCGTGGCGGA
GAGTTCTGCCGACACGCCACGGCCAAGGTTGAACAATCGCCGCGCGAATGTGCGCACGCGCACCCGGAAGCCCAAGGTCCCGCCACCGGG
ACAACAGTGTCGCCGGCCGATTTTTATGCCCTGCTCCGCCAAACCGGCCAACACCATGGTCCGGCGTTCGCGGCCTTAAGCCGGATCGTG
CGCCTGGCCGATGGTTCCGCGGAAACCGAGATCAGCATTCCCGACGAGGCGCCGCGCCATCCCGGGTATCGGCTGCACCCCGTGGTATTG
GATGCGGCATTGCAAAGCGTGGGTGCCGCGATACCCGACGGCGAGATCGCGGGGTCGGCGGAAGCCAGCTATCTGCCAGTGTCGTTCGAG
ACCATCCGGGTGTACCGCGACATCGGTCGGCACGTCAGGTGTCGTGCCCACCTGACAAACCTCGACGGCGGCACCGGAAAGATGGGCAGG
ATCGTCCTAATCAACGACGCCGGCCACATAGCGGCCGAAGTGGACGGCATCTATCTGCGTCGTGTCGAACGCCGTGCGGTACCCCTGCCA
CTAGAGCAGAAGATCTTCGATGCCGAATGGACCGAAAGCCCGATCGCAGCCGTGCCGGCTCCGGAGCCAGCTGCCGAGACGACGCGGGGA
AGTTGGCTGGTACTCGCCGATGCAACGGTGGATGCGCCAGGCAAGGCCCAGGCCAAGTCGATGGCCGACGACTTCGTGCAGCAGTGGCGC
TCACCGATGCGGCGGGTGCACACCGCCGATATCCACGACGAATCGGCGGTGCTGGCCGCATTTGCAGAAACGGCAGGCGATCCCGAGCAC
CCGCCGGTTGGCGTGGTGGTGTTCGTCGGCGGTGCCTCGAGTCGACTGGACGACGAGCTGGCGGCGGCGCGCGACACGGTGTGGTCGATC
ACCACGGTGGTTCGTGCGGTCGTCGGCACGTGGCACGGCCGATCACCGCGGCTATGGCTGGTCACCGGGGGCGGACTTTCCGTTGCCGAC
GACGAGCCGGGAACACCCGCGGCGGCTTCCTTGAAAGGGCTGGTGCGGGTGCTCGCCTTCGAGCACCCGGACATGCGCACCACCCTGGTC
GATCTGGACATCACACAAGACCCGCTGACCGCGCTGAGCGCGGAACTGCGGAATGCCGGGAGTGGGTCGCGCCATGATGACGTGATCGCG
TGGCGCGGCGAGCGCAGGTTCGTCGAACGGCTGTCGCGCGCCACGATCGATGTATCCAAAGGGCATCCGGTGGTGCGCCAGGGAGCGTCG
TACGTCGTCACCGGCGGCCTCGGCGGTCTCGGCCTGGTCGTCGCTCGTTGGCTGGTGGACCGCGGCGCCGGCCGGGTGGTGCTGGGTGGC
CGCAGCGATCCCACTGACGAGCAGTGCAACGTCCTGGCCGAACTGCAGACCCGCGCCGAGATCGTGGTTGTCCGTGGCGACGTGGCATCG
CCGGGGGTGGCAGAAAAGCTGATTGAGACGGCCCGACAGTCTGGGGGCCAATTGCGCGGCGTCGTGCACGCCGCCGCGGTCATCGAAGAC
AGCCTGGTGTTCTCTATGAGCAGGGACAACCTAGAACGGGTGTGGGCACCCAAGGCCACCGGTGCGCTGCGCATGCACGAAGCCACCGCT
GACTGCGAGCTCGACTGGTGGCTCGGATTCTCTTCCGCCGCTTCGCTATTGGGTTCTCCCGGGCAAGCGGCCTACGCGTGCGCCAGCGCG
TGGCTGGACGCGCTGGTCGGATGGCGCAGGGCATCCGGCCTGCCGGCCGCGGTGATCAACTGGGGTCCGTGGTCGGAGGTAGGCGTCGCC
CAGGCCTTGGTGGGCAGTGTTCTCGACACGATCAGTGTCGCAGAAGGCATCGAGGCTCTCGACTCATTGCTTGCCGCCGACCGGATCCGC
ACTGGAGTGGCTCGGCTGCGTGCCGATCGGGCCCTGGTCGCATTCCCGGAGATCCGCAGCATCAGCTACTTCACCCAGGTGGTCGAGGAG
CTGGACTCGGCGGGTGACCTCGGCGACTGGGGCGGGCCCGACGCGCTTGCCGACCTCGACCCGGGCGAGGCGCGGCGCGCGGTGACCGAG
CGGATGTGTGCGCGCATCGCTGCGGTGATGGGCTACACTGACCAGTCGACTGTCGAACCCGCCGTGCCCTTGGACAAGCCCCTGACCGAG
CTGGGGCTGGATTCTCTGATGGCGGTACGAATACGCAACGGCGCGCGGGCGGATTTCGGCGTGGAACCGCCGGTAGCGCTGATACTGCAA
GGCGCGTCCTTGCATGACCTGACGGCGGACTTAATGCGCCAACTCGGGCTCAATGATCCCGATCCGGCGCTCAACAACGCTGACACTATT
CGCGACCGGGCGCGCCAGCGCGCGGCAGCGCGACACGGAGCCGCGATGCGGCGCCGACCTAAACCTGAAGTACAGGGAGGATAA