| Accession | ARO:3003394 |
| Synonym(s) | Rv2043c |
| CARD Short Name | Mtub_pncA_PZA |
| Definition | pncA is a pyrazinamidase/nicotinamidase. It catalyzes the activation of pyrazinamide. Some mutation within pncA are associated with loss of enzyme activity, resulting in pyrazinamide resistance. |
| AMR Gene Family | Pyrazinamide resistant pncA |
| Drug Class | pyrazine antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Mycobacterium tuberculosisg+wgs |
| Classification | 9 ontology terms | Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + determinant of antibiotic resistance + antibiotic molecule + antibiotic resistant gene variant or mutant + pyrazine antibiotic [Drug Class] + antibiotic resistant pncA |
| Parent Term(s) | 2 ontology terms | Show + confers_resistance_to_antibiotic pyrazinamide [Antibiotic] + Pyrazinamide resistant pncA [AMR Gene Family] |
| Publications | Campbell PJ, et al. 2011. Antimicrob Agents Chemother 55(5): 2032-2041. Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. (PMID 21300839) Scorpio A, et al. 1997. Antimicrob Agents Chemother 41(3): 540-543. Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. (PMID 9055989) Lemaitre N, et al. 1999. Antimicrob Agents Chemother 43(7): 1761-1763. Characterization of new mutations in pyrazinamide-resistant strains of Mycobacterium tuberculosis and identification of conserved regions important for the catalytic activity of the pyrazinamidase PncA. (PMID 10390238) Hirano K, et al. 1998. Tuber Lung Dis 78(2): 117-122. Mutation in pncA is a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis. (PMID 9692180) Cheng SJ, et al. 2000. Antimicrob Agents Chemother 44(3): 528-532. pncA mutations as a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis: spread of a monoresistant strain in Quebec, Canada. (PMID 10681313) Hou L, et al. 2000. Epidemiol Infect 124(2): 227-232. Molecular characterization of pncA gene mutations in Mycobacterium tuberculosis clinical isolates from China. (PMID 10813147) Chan RC, et al. 2007. J Antimicrob Chemother 59(5): 866-873. Genetic and phenotypic characterization of drug-resistant Mycobacterium tuberculosis isolates in Hong Kong. (PMID 17360809) Stavrum R, et al. 2009. PLoS One 4(2): E4540. In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. (PMID 19234602) Morlock GP, et al. 2000. Antimicrob Agents Chemother 44(12): 3298-3301. Characterization of spontaneous, In vitro-selected, rifampin-resistant mutants of Mycobacterium tuberculosis strain H37Rv. (PMID 11083630) Marttila HJ, et al. 1999. Antimicrob. Agents Chemother. 43(7):1764-6 pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from northwestern Russia. (PMID 10390239) Sreevatsan S, et al. 1997. Antimicrob. Agents Chemother. 41(3):636-40 Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms. (PMID 9056006) Hannan MM, et al. 2001. J. Clin. Microbiol. 39(2):647-50 Pyrazinamide-monoresistant Mycobacterium tuberculosis in the United States. (PMID 11158123) Lee KW, et al. 2001. J. Korean Med. Sci. 16(5):537-43 Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Korea. (PMID 11641519) Mestdagh M, et al. 1999. Antimicrob. Agents Chemother. 43(9):2317-9 Relationship between pyrazinamide resistance, loss of pyrazinamidase activity, and mutations in the pncA locus in multidrug-resistant clinical isolates of Mycobacterium tuberculosis. (PMID 10471589) Sekiguchi J, et al. 2007. J. Clin. Microbiol. 45(9):2802-7 Development and evaluation of a line probe assay for rapid identification of pncA mutations in pyrazinamide-resistant mycobacterium tuberculosis strains. (PMID 17596354) Miotto P, et al. 2014. MBio 5(5):e01819-14 Mycobacterium tuberculosis pyrazinamide resistance determinants: a multicenter study. (PMID 25336456) Xia H, et al. 2020. BMC Infect. Dis. 20(1):19 Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China. (PMID 31910878) Park SK, et al. 2001. BMC Infect Dis 1:4 pncA mutations in clinical Mycobacterium tuberculosis isolates from Korea. (PMID 11429043) Rajendran A, et al. 2022. Curr Microbiol 79(11):348 Mutations Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis: A Review and Update. (PMID 36209317) 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) |
Prevalence of Mycobacterium tuberculosis pncA mutations conferring 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).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI |
|---|---|---|---|---|
| Mycobacterium tuberculosis | 20.49% | 0% | 8.58% | 0% |
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
Legend:
Published Variants:
| PMID: 21300839 | V7G Q10P Q10R D12E T47A T142M |
| PMID: 9055989 | I5S D12A D12N A26G H51Q P69R C72R L85P K96N G132S H137P C138Y V139L Q141P T142K T142M A171P -nt104:C -nt28:C -nt391:G -nt443:G -nt446:8 +nt475:C -nt71:G |
| PMID: 10390238 | +nt391:GG |
| PMID: 9692180 | G17D Y34S Y99STOP |
| PMID: 10681313 | Q10R D12A V130G,+nt420:GG A46E A46V D53A H71E H82R L85R G97S A134V C138S V139M R140S Q141P V155G T168N +nt193:A -nt301:G -nt341:C +nt420:G +nt52:G |
| PMID: 10813147 | D12A L19P Y41H P54T N118T C138Y V139A T142K Y41STOP T47P C72R L85P K96N R121P V139L S88STOP |
| PMID: 10390239 | V7G D8Y Q10K T47S D49V S66P K96E A102T A102V Y103STOP Q10STOP L116R V125D I133T Q141P R154G T160P A161P |
| PMID: 9056006 | L19P T47A P54T H57D W68L T76P L85P W119R R121P H137R V139A Y41STOP F94P +nt388:AGGTCGATG +nt397:T |
| PMID: 11158123 | I90S S104C |
| PMID: 11641519 | M1S Q10P Q10R Y103STOP Q10P,Y99D Q10STOP W119STOP L4W V7D V7F D8G V9G D12A C14R C14Y Q141STOP G23V A25E,A26G,A28D V45G A46E T47A D49A H57D F58L Y64D S67P W68R W68G W68S W68STOP T76P T76I G78D L85R L85P K96Q K96E Y103H Y103S R121P T135P D136N D136Y V139M Q141P A146T V155G L159R L172P V180F -nt151:80 -nt158:A -nt161:C +nt287:T -nt307:TACAG +nt368:18 +nt391:GG +nt392:G +nt414:G +nt465:T +nt480:TGAC +nt532:C |
| PMID: 10471589 | H51Y P62H L85R Y103H D136H H137P T142M A171T A171V L172A -nt195:68 +nt221:G -nt512:C |
| PMID: 17596354 | A3E Q10P D12A L27P H51Q P54L C72W G132S I133T D136Y M175V D53N,+nt349:CACTG +nt218:CGCATTGCCG -nt386:ATG +nt493:C |
| PMID: 25336456 | W68C Y99STOP +nt391:GG +nt392:G |
| PMID: 31910878 | Q122STOP G17S H57Q K96M T100P C138W R140G R154W V157G A161G S164P E174G L182S D63Y,T142K V9A L172P |
| PMID: 11429043 | -nt1:11 +nt382:AG +nt403:C +nt407:C -nt416:TG |
| PMID: 36209317 | D63H |
| PMID: 30337678 | G-1319A A-11C A-11G Q10P Q10R T100P Y103STOP G108STOP T114fs L116R L117fs V131fs D136fs S164STOP L4S I5T I6L I6T V7G D8E D8H D8N D12A C14R Y34D D49G D49N H51R P54L H57D H57R F58S P62S D63G S67P W68G W68R P69R H71R T76P H82R L85R G97S V128G I133T T135P D136Y C138R V139G Q141P A146E A146V L151S M175V V180A V180F V180G L182S |
ReSeqTB:
| High Confidence | Y34D L4S D49N D49G I5T H51R P54L H57D H57R F58S I6T P62S D63G S67P W68R W68G P69R V7G T76P D8N D8H H82R D8E L85R G97S T100P Q10P Q10R Y103STOP G108STOP T114fs L116R L117fs D12A V131fs I133T T135P D136Y D136fs C14R C138R V139G Q141P A146E A146V L151S S164STOP M175V V180F V180A V180G L182S A-11G |
| Moderate Confidence | H71R V128G |
| Minimal Confidence | A-11C |