The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

pncA  -  pyrazinamidase/nicotinamidase PncA

Mycobacterium tuberculosis H37Rv

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of pncA

  • In this study the nucleotide sequence of the pncA gene from 59 Mycobacterium tuberculosis clinical isolates was analyzed [1].
  • Escherichia coli isolates expressing individually five of the eight katG mutations showed loss of catalase and INH oxidation activities, and isolates carrying any of the five pncA mutations showed no pyrazinamidase activity, indicating that these mutations are associated with INH and PZA resistance, respectively [2].
  • The remaining four child cases, as well as all adult cases with detectable IS6110, showed no motility shift in pncA PCR-SSCP and had the same one-band pattern as M. tuberculosis in oxyR PCR-RFLP, suggesting TB lymphadenitis [3].
  • For comparison, 37 adult cases of tuberculous lymphadenitis were also analysed by PCR-single strand conformation polymorphism (SSCP) assay for pncA and by PCR-RFLP for oxyR [3].

High impact information on pncA

  • Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus [4].
  • PCR, together with direct DNA sequencing and PCR-restriction fragment length polymorphism (RFLP) assay, was then performed to identify polymorphic nucleotide in pncA and oxyR, respectively [3].
  • The purpose of this study was to investigate the feasibility of differentiating BCG-LA from TB in lymph nodes (LNs) by molecular analyses of two recently identified genes, pncA and oxyR [3].
  • Differentiation of BCG-induced lymphadenitis from tuberculosis in lymph node biopsy specimens by molecular analyses of pncA and oxyR [3].
  • A region of pncA was observed with a high GC content and a melting temperature approaching 90 degrees C that was initially refractory to denaturation, and a DGGE target fragment was specifically designed to detect mutations in this region [5].

Chemical compound and disease context of pncA

  • Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis in Brazil [1].
  • PZA is a prodrug that has to be converted to the active form pyrazinoic acid by pyrazinamidase (PZase) activity, encoded by the pncA gene of Mycobacterium tuberculosis, and loss of PZase activity is associated with PZA resistance [6].

Biological context of pncA

  • The rpoB and pncA mutations seen in the Turkish isolates defined six distinct genotypes amongst the six MDR isolates, while standard IS6110 typing discriminated only four [7].
  • In striking contrast, 72% of the 67 resistant organisms had pncA mutations that altered the primary amino acid sequence of pyrazinamidase [8].
  • Interestingly, 20 PZA-monoresistant strains and 1 multidrug-resistant isolate from Quebec, Canada, all had the same pncA mutation profile, consisting of an 8-nucleotide deletion and an amino acid substitution of Arg140-->Ser [6].
  • We examined the correlation of mutations in the pyrazinamidase (PZase) gene (pncA) with the pyrazinamide (PZA) resistance phenotype with 60 Mycobacterium tuberculosis isolates [9].
  • In this study, we report the development of a rapid PCR-single-strand conformation polymorphism (SSCP) assay to differentiate M. bovis from M. tuberculosis strains, based on the detection of a single characteristic point mutation in the PZase gene (pncA) of M. bovis [10].

Anatomical context of pncA

  • Rapid genotyping was performed on the sputum from a patient who presented 2 years after the initial MDR-TB outbreak and this showed rpoB and pncA genotypes identical to the other outbreak isolates [7].

Associations of pncA with chemical compounds

  • Mutations in the pncA gene were identified in 29 of 40 pyrazinamide-resistant isolates, and no pyrazinamidase activity was detected in 39 of them [1].
  • The PZase activity was measured by pyrazinamide deamination to pyrazinoic acid and ammonia, and the entire pncA sequence including the 410 bp upstream from the start codon was determined by DNA sequencing of purified PCR products [11].
  • The pzaA-complemented strain was hypersensitive to PZA (MIC, </=10 microg/ml) and nicotinamide (MIC, >/=20 microg/ml) and was also sensitive to benzamide (MIC, 20 microg/ml), unlike the wild-type and pncA-complemented mutant strains, which were highly resistant to this amide (MIC, >500 microg/ml) [12].
  • Isolates reported by local laboratories to be PZA monoresistant were sent to the state reference laboratory for repeat susceptibility testing using the BACTEC radiometric method and to the Centers for Disease Control and Prevention for pncA sequencing and PCR-restriction fragment length polymorphism (RFLP) analysis of the oxyR gene [13].
  • The oligonucleotide primers were chosen from a 500-bp genomic fragment which is well conserved in M. bovis and the pncA gene (based on M. tuberculosis-specific nucleotide polymorphism, a cytosine residue at position 169), specific for M. tuberculosis [14].

Other interactions of pncA


Analytical, diagnostic and therapeutic context of pncA


  1. Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis in Brazil. Rodrigues, V.d.e. .F., Telles, M.A., Ribeiro, M.O., Cafrune, P.I., Rossetti, M.L., Zaha, A. Antimicrob. Agents Chemother. (2005) [Pubmed]
  2. Detection of Multidrug Resistance in Mycobacterium tuberculosis. Sekiguchi, J., Miyoshi-Akiyama, T., Augustynowicz-Kopec, E., Zwolska, Z., Kirikae, F., Toyota, E., Kobayashi, I., Morita, K., Kudo, K., Kato, S., Kuratsuji, T., Mori, T., Kirikae, T. J. Clin. Microbiol. (2007) [Pubmed]
  3. Differentiation of BCG-induced lymphadenitis from tuberculosis in lymph node biopsy specimens by molecular analyses of pncA and oxyR. Yan, J.J., Chen, F.F., Jin, Y.T., Chang, K.C., Wu, J.J., Wang, Y.W., Su, I.J. J. Pathol. (1998) [Pubmed]
  4. Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Scorpio, A., Zhang, Y. Nat. Med. (1996) [Pubmed]
  5. Detection by denaturing gradient gel electrophoresis of pncA mutations associated with pyrazinamide resistance in Mycobacterium tuberculosis isolates from the United States-Mexico border region. McCammon, M.T., Gillette, J.S., Thomas, D.P., Ramaswamy, S.V., Rosas, I.I., Graviss, E.A., Vijg, J., Quitugua, T.N. Antimicrob. Agents Chemother. (2005) [Pubmed]
  6. pncA mutations as a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis: spread of a monoresistant strain in Quebec, Canada. Cheng, S.J., Thibert, L., Sanchez, T., Heifets, L., Zhang, Y. Antimicrob. Agents Chemother. (2000) [Pubmed]
  7. Simultaneous identification and typing of multi-drug-resistant Mycobacterium tuberculosis isolates by analysis of pncA and rpoB. Brown, T.J., Tansel, O., French, G.L. J. Med. Microbiol. (2000) [Pubmed]
  8. Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms. Sreevatsan, S., Pan, X., Zhang, Y., Kreiswirth, B.N., Musser, J.M. Antimicrob. Agents Chemother. (1997) [Pubmed]
  9. Phenotypic characterization of pncA mutants of Mycobacterium tuberculosis. Morlock, G.P., Crawford, J.T., Butler, W.R., Brim, S.E., Sikes, D., Mazurek, G.H., Woodley, C.L., Cooksey, R.C. Antimicrob. Agents Chemother. (2000) [Pubmed]
  10. Rapid differentiation of bovine and human tubercle bacilli based on a characteristic mutation in the bovine pyrazinamidase gene. Scorpio, A., Collins, D., Whipple, D., Cave, D., Bates, J., Zhang, Y. J. Clin. Microbiol. (1997) [Pubmed]
  11. pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates from the southeast region of Brazil. Barco, P., Cardoso, R.F., Hirata, R.D., Leite, C.Q., Pandolfi, J.R., Sato, D.N., Shikama, M.L., de Melo, F.F., Mamizuka, E.M., Campanerut, P.A., Hirata, M.H. J. Antimicrob. Chemother. (2006) [Pubmed]
  12. Expression of Mycobacterium smegmatis pyrazinamidase in Mycobacterium tuberculosis confers hypersensitivity to pyrazinamide and related amides. Boshoff, H.I., Mizrahi, V. J. Bacteriol. (2000) [Pubmed]
  13. Pyrazinamide-monoresistant Mycobacterium tuberculosis in the United States. Hannan, M.M., Desmond, E.P., Morlock, G.P., Mazurek, G.H., Crawford, J.T. J. Clin. Microbiol. (2001) [Pubmed]
  14. A multiplex-PCR for the differentiation of Mycobacterium bovis and Mycobacterium tuberculosis. Shah, D.H., Verma, R., Bakshi, C.S., Singh, R.K. FEMS Microbiol. Lett. (2002) [Pubmed]
  15. Genotypic determination of Mycobacterium tuberculosis antibiotic resistance using a novel mutation detection method, the branch migration inhibition M. tuberculosis antibiotic resistance test. Liu, Y.P., Behr, M.A., Small, P.M., Kurn, N. J. Clin. Microbiol. (2000) [Pubmed]
  16. Mycobacterium tuberculosis subsp. caprae subsp. nov.: a taxonomic study of a new member of the Mycobacterium tuberculosis complex isolated from goats in Spain. Aranaz, A., Liébana, E., Gómez-Mampaso, E., Galán, J.C., Cousins, D., Ortega, A., Blázquez, J., Baquero, F., Mateos, A., Súarez, G., Domínguez, L. Int. J. Syst. Bacteriol. (1999) [Pubmed]
  17. Characterization of pyrazinamide and ofloxacin resistance among drug resistant Mycobacterium tuberculosis isolates from Singapore. Lee, A.S., Tang, L.L., Lim, I.H., Wong, S.Y. Int. J. Infect. Dis. (2002) [Pubmed]
  18. Microarray-based pncA genotyping of pyrazinamide-resistant strains of Mycobacterium tuberculosis. Denkin, S., Volokhov, D., Chizhikov, V., Zhang, Y. J. Med. Microbiol. (2005) [Pubmed]
  19. Temperature-mediated heteroduplex analysis for detection of pncA mutations associated with pyrazinamide resistance and differentiation between Mycobacterium tuberculosis and Mycobacterium bovis by denaturing high- performance liquid chromatography. Mohamed, A.M., Bastola, D.R., Morlock, G.P., Cooksey, R.C., Hinrichs, S.H. J. Clin. Microbiol. (2004) [Pubmed]
  20. New mutations in pncA of in vitro selected pyrazinamide-resistant strains of Mycobacterium tuberculosis. Bamaga, M., Zhang, H., Wright, D.J. Microb. Drug Resist. (2001) [Pubmed]
  21. Mutation in pncA is a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis. Hirano, K., Takahashi, M., Kazumi, Y., Fukasawa, Y., Abe, C. Tuber. Lung Dis. (1997) [Pubmed]
WikiGenes - Universities