Abstract
Pyrazinamide (PZA) has remained a keystone of tuberculosis (TB) therapy, and it possesses high imperative sterilizing action that can facilitate reduction in the present chemotherapy regimen. The combination of PZA works both with first- and second-line TB drugs, notably fluoroquinolones, clofazimine, bedaquiline, delamanid and pretomanid. Pyrazinamide inhibits various targets that are involved in different cellular processes like energy production (pncA), trans-translation (rpsA) and pantothenate/coenzyme A (panD) which are required for persistence of the pathogen. It is well known that pncA gene encoding pyrazinamidase is involved in the transition of PZA into the active form of pyrazinoic acid, which implies that mutation in the pncA gene can develop PZA resistance in Mycobacterium tuberculosis (M. tuberculosis) strain leading to a major clinical and public health concern. Therefore, it is very crucial to understand its resistance mechanism and to detect it precisely to help in the management of the disease. Scope of this review is to have a deep understanding of molecular mechanism of PZA resistance with its multiple targets which would help study the association of mutations and its resistance in M. tuberculosis. This will in turn help learn about the resistance of PZA and develop more accurate molecular diagnostic tool for drug-resistant TB in future TB therapy.
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References:
Global Tuberculosis Report 2021, 2021. https://www.who.int/publications/i/item/9789240037021.
Whitfield MG, Soeters HM, Warren RM et al (2015) A global perspective on pyrazinamide resistance: systematic review and meta-analysis. PLoS ONE. https://doi.org/10.1371/journal.pone.0133869
Whitfield SEM, Dolby T et al (2016) Prevalence of pyrazinamide resistance across the spectrum of drug resistant phenotypes of Mycobacterium tuberculosis. Tuberculosis 99:128–130. https://doi.org/10.1016/j.tube.2016.05.003
Karmakar M, Rodrigues CHM, Horan K et al (2020) Structure guided prediction of Pyrazinamide resistance mutations in pncA. Sci Rep 10:1–10. https://doi.org/10.1038/s41598-020-58635-x
Global Tuberculosis Report 2020, 2020. http://apps.who.int/bookorders. (Accessed November 29, 2020).
Chang K, Yew W, Zhang Y (2018) Pyrazinamide is a two-edged sword: do WHO guidelines matter? Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.01907-17
Lamont BAD (2019) Impact of the host environment on the antitubercular action of pyrazinamide. EBioMedicine 49:374–380. https://doi.org/10.1016/j.ebiom.2019.10.014
Ramirez-Busby SM, Valafar F (2015) Systematic review of mutations in pyrazinamidase associated with pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates. Antimicrob Agents Chemother 59:5267–5277. https://doi.org/10.1128/AAC.00204-15
Chang KC, Leung CC, Yew WW et al (2012) Pyrazinamide may improve fluoroquinolone-based treatment of multidrug-resistant tuberculosis. Antimicrob Agents Chemother 56:5465–5475. https://doi.org/10.1128/AAC.01300-12
Chorine V (1945) Action of nicotinamide on bacilli of the type Mycobacterium. C R l’Acad Sci 220:150–151
Zhang Y, Mitchison D (2003) The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis 7:6–21
Yeager RL, Munroe WG, Dessau FI (1952) Pyrazinamide (aldinamide) in the treatment of pulmonary tuberculosis. Am Rev Tuberc 65:523–546
Chakraborty S, Rhee KY (2015) Tuberculosis drug development: History and evolution of the mechanism-based paradigm. Cold Spring Harb Perspect Med 5:1–11. https://doi.org/10.1101/cshperspect.a021147
Heifets LB, Lindholm-Levy PJ (1990) Is pyrazinamide bactericidal against Mycobacterium tuberculosis? Am Rev Respir Dis 141:250–252. https://doi.org/10.1164/ajrccm/141.1.250
Scorpio A, Zhang Y (1996) Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat Med 2:662–667. https://doi.org/10.1038/nm0696-662
Konno K, Feldmann FM, McDermott W (1967) Pyrazinamide susceptibility and amidase activity of tubercle bacilli. Am Rev Respir Dis 95:461–469. https://doi.org/10.1164/ARRD.1967.95.3.461
Zhang Y, Scorpio A, Nikaido H, Sun Z (1999) Role of acid pH and deficient efflux of pyrazinoic acid in unique susceptibility of Mycobacterium tuberculosis to pyrazinamide. J Bacteriol 181:2044–2049. https://doi.org/10.1128/jb.181.7.2044-2049.1999
Zhang Y, Permar S, Sun Z (2002) Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide. J Med Microbiol 51:42–49. https://doi.org/10.1099/0022-1317-51-1-42
Wade MM, Zhang Y (2006) Effects of weak acids, UV and proton motive force inhibitors on pyrazinamide activity against Mycobacterium tuberculosis in vitro. J Antimicrob Chemother 58:936–941. https://doi.org/10.1093/jac/dkl358
Scorpio A, Zhang Y (1996) Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculosis drug pyrazinamide in tubercle bacillus. Nat Med 2:662–667. https://doi.org/10.1038/nm0696-662
Sreevatsan S, Pan X, Zhang Y et al (1997) Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms. Antimicrob Agents Chemother 41:636–640. https://doi.org/10.1128/aac.41.3.636
Tan Y, Hu Z, Zhang T et al (2014) Role of pncA and rpsA gene sequencing in detection of pyrazinamide resistance in Mycobacterium tuberculosis isolates from southern China. J Clin Microbiol 52:291–297. https://doi.org/10.1128/JCM.01903-13
Akhmetova KU, Bismilda V et al (2015) Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan. Int J Tuberc Lung Dis 19:179–184. https://doi.org/10.5588/ijtld.14.0305
Köser CU, Comas I, Feuerriegel S et al (2014) Genetic diversity within Mycobacterium tuberculosis complex impacts on the accuracy of genotypic pyrazinamide drug-susceptibility assay. Tuberculosis 94:451–453. https://doi.org/10.1016/j.tube.2014.04.002
Mitchison DA (1985) The action of antituberculosis drugs in short-course chemotherapy. Tubercle 66:219–225. https://doi.org/10.1016/0041-3879(85)90040-6
Lemaitre N, Sougakoff W, Truffot-Pernot C, Jarlier V (1999) 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. Antimicrob Agents Chemother 43:1761–1763. https://doi.org/10.1128/aac.43.7.1761
Lemaitre N, Callebaut I, Frenois F et al (2001) Study of the structure-activity relationships for the pyrazinamidase (PncA) from Mycobacterium tuberculosis. Biochem J 353:453–458. https://doi.org/10.1042/0264-6021:3530453
Muthaiah M, Jagadeesan S, Ayalusamy N et al (2010) Molecular epidemiological study of pyrazinamide-resistance in clinical isolates of Mycobacterium tuberculosis from South India. Int J Mol Sci 11:2670–2680. https://doi.org/10.3390/ijms11072670
Miotto P, Cabibbe AM, Feuerriegel S et al (2014) Mycobacterium tuberculosis pyrazinamide resistance determinants: a multicenter study. MBio 5:e01819-e11814. https://doi.org/10.1128/mBio.01819-14
Wabale VR, Joshi AA, Muthaiah M, Chowdhary AS (2016) pncA gene sequence analysis for pyrazinamide resistance in Mycobacterium tuberculosis from high-incidence setting. Int J Pharm Bio Sci 7:B648–B654. https://doi.org/10.22376/ijpbs.2016.7.4.b648-654
Yadon AN, Maharaj K, Adamson JH et al (2017) A comprehensive characterization of PncA polymorphisms that confer resistance to pyrazinamide. Nat Commun. https://doi.org/10.1038/s41467-017-00721-2
Khan MT, Chinnasamy S, Cui Z et al (2020) Mechanistic analysis of A46V, H57Y, and D129N in pyrazinamidase associated with pyrazinamide resistance. Saudi J Biol Sci 27:3150–3156. https://doi.org/10.1016/j.sjbs.2020.07.015
Hameed HMA, Tan Y, Islam MM et al (2020) Detection of novel gene mutations associated with pyrazinamide resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates in Southern China. Infect Drug Resist 13:217–227. https://doi.org/10.2147/IDR.S230774
Whitfield SHM, Warren RM et al (2015) A global perspective on pyrazinamide resistance: systematic review and meta-analysis. PLoS ONE 10:1–16. https://doi.org/10.1371/journal.pone.0133869
Shi W, Zhang X, Jiang X et al (2011) Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science (1979) 333:1630–1632. https://doi.org/10.1126/science.1208813
Dillon NA, Peterson ND, Feaga HA et al (2017) Anti-tubercular activity of pyrazinamide is independent of trans-translation and RpsA. Sci Rep 7:1–8. https://doi.org/10.1038/s41598-017-06415-5
Werngren J, Alm E, Mansjö M (2017) Non-pncA gene-mutated but pyrazinamide-resistant Mycobacterium tuberculosis: why is that? J Clin Microbiol 55:1920–1927. https://doi.org/10.1128/JCM.02532-16
Alexander DC, Ma JH, Guthrie JL et al (2012) Gene sequencing for routine verification of pyrazinamide resistance in Mycobacterium tuberculosis: a role for pncA but not rpsA. J Clin Microbiol 50:3726–3728. https://doi.org/10.1128/JCM.00620-12
Liu W, Chen J, Shen Y et al (2018) Phenotypic and genotypic characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis clinical isolates in Hangzhou, China. Clin Microbiol Infect 24:1016.e1-1016.e5. https://doi.org/10.1016/j.cmi.2017.12.012
Yang J, Liu Y, Bi J et al (2015) Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide. Mol Microbiol 95:791–803. https://doi.org/10.1111/mmi.12892
Gu Y, Yu X, Jiang G et al (2016) Pyrazinamide resistance among multidrug-resistant tuberculosis clinical isolates in a national referral centre of China and its correlations with pncA, rpsA, and panD gene mutations. Diagn Microbiol Infect Dis 84:207–211. https://doi.org/10.1016/j.diagmicrobio.2015.10.017
Khan M, Malik SI, Bhatti AI et al (2018) Pyrazinamide-resistant Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa and rpsA mutations—PubMed. J Biol Regul Homeost Agents 32:705
Shi W, Cui P, Niu H et al (2019) Introducing RpsA point mutations 438A and D123A into the chromosome of Mycobacterium tuberculosis confirms their role in causing resistance to pyrazinamide. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.02681-18
Shi SuR, Zheng D et al (2020) Pyrazinamide resistance and mutation patterns among multidrug-resistant Mycobacterium tuberculosis from Henan Province. Infect Drug Resist 13:2929–2941. https://doi.org/10.2147/IDR.S260161
Vallejos-Sánchez K, Lopez JM, Antiparra R et al (2020) Mycobacterium tuberculosis ribosomal protein S1 (RpsA) and variants with truncated C-terminal end show absence of interaction with pyrazinoic acid. Sci Rep 10:1–11. https://doi.org/10.1038/s41598-020-65173-z
Scorpio A, Lindholm-Levy P, Heifets L et al (1997) Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 41:540–543. https://doi.org/10.1128/aac.41.3.540
Klemens SP, Sharpe CA, Cynamon MH (1996) Activity of pyrazinamide in a murine model against Mycobacterium tuberculosis isolates with various levels of in vitro susceptibility. Antimicrob Agents Chemother 40:14–16
Sambandamurthy VK, Wang X, Chen B et al (2002) A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis. Nat Med 8:1171–1174. https://doi.org/10.1038/nm765
Zhang S, Chen J, Shi W et al (2013) Mutations in panD encoding aspartate decarboxylase are associated with pyrazinamide resistance in Mycobacterium tuberculosis. Emerging Microbes Infect. https://doi.org/10.1038/emi.2013.38
Shi W, Chen J, Feng J et al (2014) Aspartate decarboxylase (PanD) as a new target of pyrazinamide in Mycobacterium tuberculosis. Emerging Microbes Infect 3:1–8. https://doi.org/10.1038/emi.2014.61
Dillon NA, Peterson ND, Rosen BC, Baughn AD (2014) Pantothenate and pantetheine antagonize the antitubercular activity of pyrazinamide. Antimicrob Agents Chemother 58:7258–7263. https://doi.org/10.1128/AAC.04028-14
Gopal P, Yee M, Sarathy J et al (2016) Pyrazinamide resistance is caused by two distinct mechanisms: prevention of coenzyme a depletion and loss of virulence factor synthesis. ACS Infect Dis 2:616–626. https://doi.org/10.1021/acsinfecdis.6b00070
Sun Q, Li X, Perez LM et al (2020) The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD. Nat Commun 11:1–7. https://doi.org/10.1038/s41467-019-14238-3
Gopal P, Tasneen R, Yee M et al (2017) In vivo-selected pyrazinoic acid-resistant Mycobacterium tuberculosis strains harbor missense mutations in the aspartate decarboxylase PanD and the Unfoldase ClpC1. ACS Infect Dis 3:492–501. https://doi.org/10.1021/acsinfecdis.7b00017
Lee H, Suh JW (2016) Anti-tuberculosis lead molecules from natural products targeting Mycobacterium tuberculosis ClpC1. J Ind Microbiol Biotechnol 43:205–212. https://doi.org/10.1007/s10295-015-1709-3
Zhang S, Chen J, Shi W et al (2017) Mutation in clpC1 encoding an ATP-dependent ATPase involved in protein degradation is associated with pyrazinamide resistance in Mycobacterium tuberculosis. Emerging Microbes Infect 6:e8. https://doi.org/10.1038/emi.2017.1
Yee M, Gopal P, Dick T (2017) Missense mutations in the unfoldase ClpC1 of the caseinolytic protease complex are associated with pyrazinamide resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 61:1–6. https://doi.org/10.1128/AAC.02342-16
Modlin SJ, Marbach T, Werngren J et al (2021) Atypical genetic basis of pyrazinamide resistance in monoresistant Mycobacterium tuberculosis. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.01916-20
Shi W, Chen J, Zhang S et al (2018) Identification of novel mutations in LprG (rv1411c), rv0521, rv3630, rv0010c, ppsC, and cyp128 associated with pyrazinoic acid/pyrazinamide resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 62:e00430
He L, Cui P, Shi W et al (2019) Pyrazinoic acid inhibits the bifunctional enzyme (Rv2783) in Mycobacterium tuberculosis by competing with tmRNA. Pathogens 8:10–15. https://doi.org/10.3390/pathogens8040230
World Health Organization (2021) Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. WHO, Geneva
Zhang Y, Zhang H, Sun Z (2003) Susceptibility of Mycobacterium tuberculosis to weak acids. J Antimicrob Chemother 52:56–60. https://doi.org/10.1093/jac/dkg287
Singh P, Wesley C, Jadaun GPS et al (2007) Comparative evaluation of Löwenstein-Jensen proportion method, BacT/ALERT 3D system, and enzymatic pyrazinamidase assay for pyrazinamide susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol 45:76–80. https://doi.org/10.1128/JCM.00951-06
Banu S, Rahman SMM, Khan MSR et al (2014) Discordance across several methods for drug susceptibility testing of drug-resistant Mycobacterium tuberculosis Isolates in a single laboratory. J Clin Microbiol 52:156. https://doi.org/10.1128/JCM.02378-13
Zhou M, Geng X, Chen J et al (2011) Rapid colorimetric testing for pyrazinamide susceptibility of M. tuberculosis by a PCR-Based In-Vitro synthesized Pyrazinamidase method. PLoS ONE. https://doi.org/10.1371/journal.pone.0027654
Cui Z, Wang J, Lu J et al (2013) Evaluation of methods for testing the susceptibility of clinical Mycobacterium tuberculosis isolates to pyrazinamide. J Clin Microbiol 51:1374–1380. https://doi.org/10.1128/JCM.03197-12/FORMAT/EPUB
Werngren J, Sturegård E, Juréen P et al (2012) Reevaluation of the critical concentration for drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide using wild-type MIC distributions and pncA gene sequencing. Antimicrob Agents Chemother 56:1253–1257. https://doi.org/10.1128/AAC.05894-11
Aono A, Chikamatsu K, Yamada H et al (2014) Association between pncA gene mutations, pyrazinamidase activity, and pyrazinamide susceptibility testing in Mycobacterium tuberculosis. Antimicrob Agents Chemother 58:4928–4930. https://doi.org/10.1128/AAC.02394-14
Willby MJ, Wijkander M, Havumaki J et al (2018) Detection of Mycobacterium tuberculosis pncA mutations by the Nipro Genoscholar PZA-TB II assay compared to conventional sequencing. Antimicrob Agents Chemother 62:e01871-e11817. https://doi.org/10.1128/AAC.01871-17
Streicher EM, Maharaj K, York T et al (2014) Rapid sequencing of the Mycobacterium tuberculosis pncA gene for detection of pyrazinamide susceptibility. J Clin Microbiol 52:4056–4057. https://doi.org/10.1128/JCM.02438-14
Tam KKG, Leung KSS, Siu GKH et al (2019) Direct detection of pyrazinamide resistance in Mycobacterium tuberculosis by use of pncA PCR sequencing. J Clin Microbiol. https://doi.org/10.1128/JCM.00145-19
Nasr-esfahani B, Moghim S, Salehi M, Keikha M (2021) Evaluating the frequency of resistance to pyrazinamide among drug-resistant strains of mycobacterium tuberculosis in Isfahan, Iran. Arch Clin infect Dis. https://doi.org/10.5812/archcid.101092.Research
Cabibbe AM, Walker TM, Niemann S, Cirillo DM (2018) Whole genome sequencing of Mycobacterium tuberculosis. Eur Respir J 52:1–5. https://doi.org/10.1183/13993003.01163-2018
Maningi NE, Daum LT, Rodriguez JD et al (2015) Improved detection by next-generation sequencing of pyrazinamide resistance in Mycobacterium tuberculosis isolates. J Clin Microbiol 53:3779–3783. https://doi.org/10.1128/JCM.01179-15
Daum LT, Konstantynovska OS, Solodiankin OS et al (2019) Characterization of novel Mycobacterium tuberculosis pncA gene mutations in clinical isolates from the Ukraine. Diagn Microbiol Infect Dis 93:334–338. https://doi.org/10.1016/j.diagmicrobio.2018.10.018
Hou L, Osei-Hyiaman D, Zhang Z et al (2000) Molecular characterization of pncA gene mutations in Mycobacterium tuberculosis clinical isolates from China. Epidemiol Infect 124:227–232. https://doi.org/10.1017/S0950268899003635
Lee KW, Lee J-M, Jung K-S (2001) Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Korea. J Korean Med Sci. https://doi.org/10.3346/jkms.2001.16.5.537
Bishop KS, Blumberg L, Trollip AP et al (2001) Characterisation of the pncA gene in Mycobacterium tuberculosis isolates from Gauteng, South Africa. Int J Tuberc Lung Dis 5:952–957
Huang TS, Shin-Jung Lee S, Tu HZ et al (2003) Correlation between Pyrazinamide Activity and pncA Mutations in Mycobacterium tuberculosis Isolates in Taiwan. Antimicrob Agents Chemother 47:3672–3673. https://doi.org/10.1128/AAC.47.11.3672-3673.2003
Miyagi C, Yamane N, Yogesh B et al (2004) Genetic and phenotypic characterization of pyrazinamide-resistant Mycobacterium tuberculosis complex isolates in Japan. Diagn Microbiol Infect Dis 48:111–116. https://doi.org/10.1016/j.diagmicrobio.2003.09.013
Sumnienski Rodrigues VDF, Telles MA, Ribeiro MO et al (2005) Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis in Brazil. Antimicrob Agents Chemother 49:444–446. https://doi.org/10.1128/AAC.49.1.444-446.2005
GE Louw RWPD (2006) Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients. Int J Tuberc Lung Dis 10:802–807
Pandey S, Newton S, Upton A et al (2009) Characterisation of pncA mutations in clinical Mycobacterium tuberculosis isolates in New Zealand. Pathology 41:582–584. https://doi.org/10.1080/00313020903071587
Jonmalung J, Prammananan T, Leechawengwongs M, Chaiprasert A (2010) Surveillance of pyrazinamide susceptibility among multidrug-resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand. BMC Microbiol 10:223. https://doi.org/10.1186/1471-2180-10-223
Chiu YC, Huang SF, Yu KW et al (2011) Characteristics of pncA mutations in multidrug-resistant tuberculosis in Taiwan. BMC Infect Dis 11:240. https://doi.org/10.1186/1471-2334-11-240
Campbell PJ, Morlock GP, Sikes RD et al (2011) Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. Antimicrob Agents Chemother 55:2032–2041. https://doi.org/10.1128/AAC.01550-10
Bhuju S, de Souza Fonseca L, Marsico AG et al (2013) Mycobacterium tuberculosis isolates from Rio de Janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pncA gene. Infect Genet Evol 19:1–6. https://doi.org/10.1016/j.meegid.2013.06.008
Jnawali HN, Hwang SC, Park YK et al (2013) Characterization of mutations in multi- and extensive drug resistance among strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea. Diagn Microbiol Infect Dis 76:187–196. https://doi.org/10.1016/j.diagmicrobio.2013.02.035
Maslov DA, Zaîchikova MV, Chernousova LN et al (2015) Resistance to pyrazinamide in Russian Mycobacterium tuberculosis isolates: pncA sequencing versus Bactec MGIT 960. Tuberculosis 95:608–612. https://doi.org/10.1016/j.tube.2015.05.013
Reena K, Kumar P, Shanthi V (2016) Pyrazinamide drug resistance patterns in multi drug resistant Mycobacterium tuberculosis isolates from India. J Pure Appl Microbiol 10:2153–2163
Huy NQ, Lucie C, Hoa TTT et al (2017) Molecular analysis of pyrazinamide resistance in Mycobacterium tuberculosis in Vietnam highlights the high rate of pyrazinamide resistance-associated mutations in clinical isolates. Emerging Microbes Infect. https://doi.org/10.1038/emi.2017.73
Rahman A, Ferdous SS, Ahmed S et al (2017) Pyrazinamide susceptibility and pncA mutation profiles of Mycobacterium tuberculosis among multidrug-resistant tuberculosis patients in Bangladesh. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00511-17
Khan M, Malik S, Ali S et al (2019) PZAR and mutations in pncA among isolates of MTB from Khyber Pakhtunkhwa, Pakistan. RSC Adv. https://doi.org/10.1186/s12879-019-3764-2
Xia Q, Zhao LL, Li F et al (2015) Phenotypic and genotypic characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Zhejiang, China. Antimicrob Agents Chemother 59:1690–1695. https://doi.org/10.1128/AAC.04541-14
Naluyange R, Mboowa G, Komakech K et al (2020) High prevalence of phenotypic pyrazinamide resistance and its association with pncA gene mutations in Mycobacterium tuberculosis isolates from Uganda. PLoS ONE 15:1–8. https://doi.org/10.1371/journal.pone.0232543
Li K, Yang Z, Gu J et al (2021) Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China. Front Microbiol 11:1–10. https://doi.org/10.3389/fmicb.2020.594171
Che Y, Bo D, Lin X et al (2021) Phenotypic and molecular characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Ningbo, China. BMC Infect Dis 21:1–8. https://doi.org/10.1186/s12879-021-06306-1
Acknowledgements
The authors would like to thank the Director of ICMR-National Institute for Research in Tuberculosis Dr. C. Padmapriyadarsini and Dr. M. Muniyandi for organizing “Scientific Manuscript Writing Workshop”. The valuable inputs of Dr. Radha Gopalaswamy while writing the manuscript is duly appreciated and the help rendered by Ms. Harini Ramanujam and Ms. Ranjani Singaraj is acknowledged.
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This study is funded by Indian Council for Medical Research (ICMR) (Grant ID 2017-2590).
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Rajendran, A., Palaniyandi, K. Mutations Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis: A Review and Update. Curr Microbiol 79, 348 (2022). https://doi.org/10.1007/s00284-022-03032-y
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DOI: https://doi.org/10.1007/s00284-022-03032-y