Mycobacterium tuberculosis clpC1 with mutation conferring resistance to pyrazinamide

Accession ARO:3004957
CARD Short NameMtub_clpC1_PZA
DefinitionMutations that occur in clpC1 that result in or contribute to antibiotic resistance to pyrazinamide.
AMR Gene Familypyrazinamide resistant clpC1
Drug Classpyrazine antibiotic
Resistance Mechanismantibiotic target alteration
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic pyrazinamide [Antibiotic]
+ pyrazinamide resistant clpC1 [AMR Gene Family]
Publications

Gopal P, et al. 2017. ACS Infect Dis 3(7):492-501 In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1. (PMID 28271875)

Modlin SJ, et al. 2021. Antimicrob Agents Chemother 65(6): Atypical Genetic Basis of Pyrazinamide Resistance in Monoresistant Mycobacterium tuberculosis. (PMID 33722890)

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 clpC1 with mutation conferring resistance to pyrazinamide 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): 1600

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
G258Vsingle resistance variantno dataReSeqTB-Minimalno datano data

>gb|YP_177995.1|-|Mycobacterium tuberculosis clpC1 with mutation conferring resistance to pyrazinamide [Mycobacterium tuberculosis H37Rv]
MFERFTDRARRVVVLAQEEARMLNHNYIGTEHILLGLIHEGEGVAAKSLESLGISLEGVR
SQVEEIIGQGQQAPSGHIPFTPRAKKVLELSLREALQLGHNYIGTEHILLGLIREGEGVA
AQVLVKLGAELTRVRQQVIQLLSGYQGKEAAEAGTGGRGGESGSPSTSLVLDQFGRNLTA
AAMEGKLDPVIGREKEIERVMQVLSRRTKNNPVLIGEPGVGKTAVVEGLAQAIVHGEVPE
TLKDKQLYTLDLGSLVAGSRYRGDFEERLKKVLKEINTRGDIILFIDELHTLVGAGAAEG
AIDAASILKPKLARGELQTIGATTLDEYRKYIEKDAALERRFQPVQVGEPTVEHTIEILK
GLRDRYEAHHRVSITDAAMVAAATLADRYINDRFLPDKAIDLIDEAGARMRIRRMTAPPD
LREFDEKIAEARREKESAIDAQDFEKAASLRDREKTLVAQRAEREKQWRSGDLDVVAEVD
DEQIAEVLGNWTGIPVFKLTEAETTRLLRMEEELHKRIIGQEDAVKAVSKAIRRTRAGLK
DPKRPSGSFIFAGPSGVGKTELSKALANFLFGDDDALIQIDMGEFHDRFTASRLFGAPPG
YVGYEEGGQLTEKVRRKPFSVVLFDEIEKAHQEIYNSLLQVLEDGRLTDGQGRTVDFKNT
VLIFTSNLGTSDISKPVGLGFSKGGGENDYERMKQKVNDELKKHFRPEFLNRIDDIIVFH
QLTREEIIRMVDLMISRVAGQLKSKDMALVLTDAAKALLAKRGFDPVLGARPLRRTIQRE
IEDQLSEKILFEEVGPGQVVTVDVDNWDGEGPGEDAVFTFTGTRKPPAEPDLAKAGAHSA
GGPEPAAR



>gb|NC_000962.3|-|4038158-4040704|Mycobacterium tuberculosis clpC1 with mutation conferring resistance to pyrazinamide [Mycobacterium tuberculosis H37Rv]
ATGTTCGAACGATTTACCGACCGTGCCCGCAGGGTCGTCGTCCTGGCTCAGGAAGAGGCCAGGATGCTCAACCACAACTACATCGGCACC
GAGCACATTCTTTTAGGCCTGATCCATGAAGGGGAAGGCGTTGCCGCCAAGTCACTGGAGTCGTTGGGGATCTCGCTGGAAGGTGTGCGC
AGTCAGGTCGAGGAGATCATCGGCCAGGGCCAGCAGGCGCCGTCTGGGCACATTCCGTTTACCCCCCGCGCCAAAAAGGTCCTCGAGCTG
AGCTTGCGTGAAGCGCTGCAGCTTGGCCACAACTACATCGGGACCGAACACATTTTGCTGGGCCTCATCCGAGAGGGTGAAGGCGTGGCC
GCCCAGGTGCTGGTCAAGCTGGGCGCCGAGCTGACCCGGGTGCGCCAGCAGGTGATCCAGCTGCTCTCCGGTTACCAAGGCAAGGAGGCC
GCCGAAGCCGGCACCGGCGGCCGCGGGGGAGAGTCCGGCTCTCCGTCTACGTCCTTGGTGCTCGACCAGTTCGGCCGCAACCTCACGGCG
GCGGCGATGGAAGGCAAACTGGACCCGGTCATCGGCCGCGAGAAGGAAATCGAGCGGGTCATGCAGGTGCTCTCTCGGCGCACCAAGAAC
AACCCGGTGCTGATCGGCGAGCCCGGCGTCGGCAAGACCGCGGTCGTCGAAGGACTGGCGCAGGCCATCGTGCACGGCGAGGTGCCCGAG
ACGCTCAAGGACAAGCAGCTCTACACGCTGGATCTGGGATCGCTGGTGGCGGGTAGCCGCTACCGCGGTGACTTCGAGGAACGCCTCAAG
AAGGTGCTCAAGGAGATCAACACCCGCGGTGACATCATCCTGTTTATCGACGAGCTGCACACCTTGGTCGGTGCTGGAGCCGCCGAGGGC
GCGATCGACGCCGCCTCGATCCTGAAACCGAAGCTCGCTCGCGGTGAACTGCAAACGATCGGCGCCACCACGCTCGACGAATACCGCAAG
TACATCGAGAAGGACGCCGCGCTGGAGCGCCGCTTCCAGCCGGTGCAGGTGGGTGAGCCGACGGTGGAGCACACCATCGAGATCCTCAAG
GGCCTGCGGGACCGGTACGAGGCGCACCACCGGGTGTCGATCACCGATGCGGCGATGGTGGCCGCCGCGACCCTGGCCGACCGCTACATC
AACGACCGGTTCCTGCCCGACAAGGCGATCGACCTGATCGACGAGGCGGGTGCTCGGATGCGGATTCGTCGCATGACCGCACCGCCAGAC
CTACGCGAGTTCGATGAGAAGATCGCCGAGGCTCGTCGGGAGAAGGAATCGGCTATCGACGCCCAGGACTTCGAGAAGGCCGCCAGCCTG
CGCGACCGGGAGAAGACACTGGTCGCACAGCGTGCTGAGCGCGAAAAGCAGTGGCGTTCAGGCGATCTTGACGTGGTCGCGGAGGTCGAC
GACGAGCAGATCGCCGAGGTGCTGGGCAACTGGACCGGTATCCCGGTGTTCAAGCTCACCGAGGCCGAGACCACCCGGCTGTTGCGGATG
GAAGAAGAGCTGCACAAGCGGATCATCGGGCAAGAGGACGCCGTCAAGGCCGTTTCCAAGGCCATCCGGCGTACCCGGGCCGGGCTGAAA
GACCCCAAGCGCCCGTCGGGCTCGTTCATCTTCGCCGGCCCGTCCGGTGTCGGTAAGACCGAACTGTCCAAGGCGCTGGCCAACTTCTTG
TTCGGTGACGACGACGCGCTTATTCAGATTGACATGGGTGAATTCCACGACCGGTTCACCGCGTCGCGGCTATTCGGCGCGCCGCCCGGA
TACGTCGGCTACGAGGAGGGCGGCCAACTCACCGAGAAGGTGCGGCGCAAGCCGTTCTCGGTGGTGCTGTTCGACGAGATCGAGAAGGCG
CATCAGGAGATCTACAACAGCCTGCTGCAGGTGCTCGAGGATGGCCGGCTCACCGACGGGCAGGGCCGCACGGTGGACTTCAAGAACACC
GTGCTGATCTTTACGTCCAATCTGGGCACCTCCGACATCTCTAAGCCGGTCGGTCTGGGCTTTTCCAAGGGCGGCGGTGAGAACGACTAC
GAGCGGATGAAACAGAAGGTCAACGACGAGCTGAAGAAACACTTCCGCCCGGAGTTCCTCAACCGCATCGACGACATCATCGTCTTCCAC
CAGCTGACCCGCGAGGAGATCATCCGGATGGTCGACCTGATGATCAGCCGGGTCGCCGGCCAGCTCAAGAGCAAGGACATGGCGCTGGTG
CTGACCGATGCGGCCAAGGCGCTGCTGGCCAAGCGTGGCTTCGACCCGGTGTTGGGGGCCCGCCCGTTGCGGCGCACCATCCAGCGTGAG
ATCGAAGATCAGCTCTCGGAGAAGATCCTCTTCGAGGAGGTCGGGCCGGGTCAGGTGGTCACCGTCGACGTGGACAACTGGGACGGTGAA
GGTCCCGGCGAGGACGCGGTGTTCACCTTCACCGGTACCCGCAAGCCGCCGGCCGAGCCGGATCTGGCCAAGGCTGGAGCGCACAGCGCG
GGCGGCCCGGAGCCGGCCGCGCGGTAG

Curator Acknowledgements
Curator Description Most Recent Edit