513
Views
19
CrossRef citations to date
0
Altmetric
Reviews

Novel insights into the pharmacometabonomics of first-line tuberculosis drugs relating to metabolism, mechanism of action and drug-resistance

ORCID Icon & ORCID Icon
Pages 466-481 | Received 01 Oct 2018, Accepted 11 Dec 2018, Published online: 07 Jan 2019

References

  • Ahmad S, Mokaddas E. 2009. Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis. Respir Med. 103:1777–1790.
  • Alifano P, Palumbo C, Pasanisi D, Talà A. 2015. Rifampicin-resistance, rpoB polymorphism and RNA polymerase genetic engineering. J Biotechnol. 202:60–77.
  • Aono A, Chikamatsu K, Yamada H, Kato T, Mitarai S. 2014. Association between pncA gene mutations, pyrazinamidase activity, and pyrazinamide susceptibility testing in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 58:4928–4930.
  • Arbex MA, Varella MCL, Siqueira HRd, Mello FAFd. 2010. Antituberculosis drugs: Drug interactions, adverse effects, and use in special situations-part 1: first-line drugs. J Bras Pneumol. 36:626–640.
  • Becker C, Dressman JB, Amidon GL, Junginger HE, Kopp S, Midha KK, Shah VP, Stavchansky S, Barends DM. 2008. Biowaiver monographs for immediate release solid oral dosage forms: ethambutol dihydrochloride. J Pharm Sci. 97:1350–1360.
  • Bisson GP, Mehaffy C, Broeckling C, Prenni J, Rifat D, Lun DS, Burgos M, Weissman D, Karakousis PC, Dobos K. 2012. Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampicin-resistant, rpoB-mutant Mycobacterium tuberculosis. J Bacteriol. 194:6441–6452.
  • Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, Fujiwara P, Grzemska M, Hopewell PC, Iseman MD, et al. 2003. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 167:603.
  • Boshoff HI, Mizrahi V, Barry CE. 2002. Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J Bacteriol. 184:2167–2172.
  • Bugrim A, Nikolskaya T, Nikolsky Y. 2004. Early prediction of drug metabolism and toxicity: systems biology approach and modeling. Drug Discov Today. 9:127–135.
  • Cho J-Y, Kang DW, Ma X, Ahn S-H, Krausz KW, Luecke H, Idle JR, Gonzalez FJ. 2009. Metabolomics reveals a novel vitamin E metabolite and attenuated vitamin E metabolism upon PXR activation. J Lipid Res. 50:924–937.
  • Cunningham K, Claus SP, Lindon JC, Holmes E, Everett JR, Nicholson JK, Coen M. 2012. Pharmacometabonomic characterization of xenobiotic and endogenous metabolic phenotypes that account for inter-individual variation in isoniazid-induced toxicological response. J Proteome Res. 11:4630–4642.
  • Da Silva PEA, Palomino JC. 2011. Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs. J Antimicrob Chemother. 66:1417–1430.
  • Das MK, Arya R, Debnath S, Debnath R, Lodh A, Bishwal SC, Das A, Nanda RK. 2016. Global urine metabolomics in patients treated with first-line tuberculosis drugs and identification of a novel metabolite of ethambutol. Antimicrob Agents Chemother. 60:2257–2264.
  • De Villiers L, Loots D. 2013. Using metabolomics for elucidating the mechanisms related to tuberculosis treatment failure. CMB. 1:306–317.
  • Du Preez I, Loots D. 2012. Altered fatty acid metabolism due to rifampicin-resistance conferring mutations in the rpoB gene of Mycobacterium tuberculosis: mapping the potential of pharmaco-metabolomics for global health and personalized medicine. OMICS. 16:596–603.
  • Du Preez I, Loots D. 2013. New sputum metabolite markers implicating adaptations of the host to Mycobacterium tuberculosis, and vice versa. Tuberculosis (Edinb)). 93:330–337.
  • Fiehn O. 2002. Metabolomics-the link between genotypes and phenotypes. Plant Mol Biol. 48:155–171.
  • Floss HG, Yu T-W. 2005. Rifamycin-mode of action, resistance, and biosynthesis. Chem Rev. 105:621–632.
  • Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJ. 2006. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science. 312:1944–1946.
  • Giri A, Gupta S, Safi H, Narang A, Shrivastava K, Kumar Sharma N, Lingaraju S, Hanif M, Bhatnagar A, Menon B, et al. 2018. Polymorphisms in Rv3806c (ubiA) and the upstream region of embA in relation to ethambutol resistance in clinical isolates of Mycobacterium tuberculosis from North India. Tuberculosis. 108:41–46.
  • Guengerich FP. 1999. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol. 39: 1–17.
  • He L, Wang X, Cui P, Jin J, Chen J, Zhang W, Zhang Y. 2015. ubiA (Rv3806c ) encoding DPPR synthase involved in cell wall synthesis is associated with ethambutol resistance in Mycobacterium tuberculosis. Tuberculosis (Edinb). 95:149–154.
  • Jadaun GPS, Das R, Upadhyay P, Chauhan DS, Sharma VD, Katoch VM. 2009. Role of embCAB gene mutations in ethambutol resistance in Mycobacterium tuberculosis isolates from India. Int J Antimicrob Agents. 33:483–486.
  • Kim B, Moon J-Y, Choi MH, Yang HH, Lee S, Lim KS, Yoon SH, Yu K-S, Jang I-J, Cho J-Y. 2013. Global metabolomics and targeted steroid profiling reveal that rifampin, a strong human PXR activator, alters endogenous urinary steroid markers. J Proteome Res. 12:1359–1368.
  • Klein DJ, Boukouvala S, McDonagh EM, Shuldiner SR, Laurieri N, Thorn CF, Altman RB, Klein TE. 2016. PharmGKB summary: isoniazid pathway, pharmacokinetics. Pharmacogenet Genomics. 26:436–444.
  • Koch A, Mizrahi V, Warner DF. 2014. The impact of drug resistance on Mycobacterium tuberculosis physiology: what can we learn from rifampicin? Emerg Microbes Infect. 3:e17.
  • Koen N, D, Preez I, Loots D. 2016. Chapter 3, Metabolomics and personalized medicine. In: Donev R, editor. Advances in protein chemistry and structural biology. London, UK: Elsevier; p. 53–78.
  • Lahiri N, Shah RR, Layre E, Young D, Ford C, Murray MB, Fortune SM, Moody DB. 2016. Rifampin resistance mutations are associated with broad chemical remodeling of Mycobacterium tuberculosis. J Biol Chem. 291:14248–14256.
  • Lan K, Jia W. 2010. An integrated metabolomics and pharmacokinetics strategy for multi-component drugs evaluation. Curr Drug Metab. 11:105–114.
  • Li F, Lu J, Cheng J, Wang L, Matsubara T, Csanaky IL, Klaassen CD, Gonzalez FJ, Ma X. 2013. Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy. Nat Med. 19:418–420.
  • Li F, Miao Y, Zhang L, Neuenswander SA, Douglas JT, Ma X. 2011. Metabolomic analysis reveals novel isoniazid metabolites and hydrazones in human urine. Drug Metab Pharmacokinet. 26:569–576.
  • Liu K, Li F, Lu J, Gao Z, Klaassen CD, Ma X. 2014. Role of CYP3A in isoniazid metabolism in vivo. Drug Metab Pharmacokinet. 29:219–222.
  • Loots D. 2014. An altered Mycobacterium tuberculosis metabolome induced by katG mutations resulting in isoniazid resistance. Antimicrob Agents Chemother. 58:2144–2149.
  • Loots D. 2016. New insights into the survival mechanisms of rifampicin-resistant Mycobacterium tuberculosis. J Antimicrob Chemother. 71:655–660.
  • Luies L, Van Reenen M, Ronacher K, Walzl G, Loots D. 2017. Predicting tuberculosis treatment outcome using metabolomics. Biomarkers Med. 11:1057–1067.
  • Madsen R, Lundstedt T, Trygg J. 2010. Chemometrics in metabolomics-a review in human disease diagnosis. Anal Chim Acta. 659:23–33.
  • Mahapatra S, Woolhiser LK, Lenaerts AJ, Johnson JL, Eisenach KD, Joloba ML, Boom WH, Belisle JT. 2012. A novel metabolite of antituberculosis therapy demonstrates host activation of isoniazid and formation of the isoniazid-NAD + adduct. Antimicrob Agents Chemother. 56:28–35.
  • Man DK-W, Kanno T, Manzo G, Robertson BD, Lam JK, Mason AJ. Forthcoming 2018. Rifampicin or capreomycin induced remodelling of the Mycobacterium smegmatis mycolic acid layer is mitigated in synergistic combinations with cationic antimicrobial peptides.
  • Minnikin DE, Lee O-C, Wu HH, Nataraj V, Donoghue HD, Ridell M, Watanabe M, Alderwick L, Bhatt A, Besra GS. 2015. Pathophysiological implications of cell envelope structure in Mycobacterium tuberculosis and related taxa. In: Wellman Ribón, editor. Tuberculosis - Expanding Knowledge. London, UK: IntechOpen;145–175.
  • Mirsaeidi M, Banoei MM, Winston BW, Schraufnagel DE. 2015. Metabolomics: applications and promise in mycobacterial disease. Ann Am Thorac Soc. 12:1278–1287.
  • Nakajima A, Fukami T, Kobayashi Y, Watanabe A, Nakajima M, Yokoi T. 2011. Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine. Biochem Pharmacol. 82:1747–1756.
  • Olah TV, McLoughlin DA, Gilbert JD. 1997. The simultaneous determination of mixtures of drug candidates by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry as an in vivo drug screening procedure. Rapid Commun Mass Spectrom. 11:17–23.
  • Pang Y, Lu J, Wang Y, Song Y, Wang S, Zhao Y. 2013. Study of the rifampin monoresistance mechanism in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 57:893–900.
  • Papastavros T, Dolovich LR, Holbrook A, Whitehead L, Loeb M. 2002. Adverse events associated with pyrazinamide and levofloxacin in the treatment of latent multidrug-resistant tuberculosis. Can Med Assoc J. 167:131–136.
  • Peets E, Sweeney W, Place V, Buyske D. 1965. The absorption, excretion, and metabolic fate of ethambutol in man. Am Rev Respir Dis. 91:51–58.
  • Rae JM, Johnson MD, Lippman ME, Flockhart DA. 2001. Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays. J Pharmacol Exp Ther. 299:849–857.
  • Ramappa V, Aithal GP. 2013. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. J Clin Exp Hepatol. 3:37–49.
  • Ramirez-Busby S, Rodwell T, Fink L, Catanzaro D, Jackson R, Pettigrove M, Catanzaro A, Valafar F. 2017. A multinational analysis of mutations and heterogeneity in PZase, RpsA, and PanD associated with pyrazinamide resistance in M/XDR Mycobacterium tuberculosis. Sci Rep. 7:3790.
  • Ramirez-Busby S, Valafar F. 2015. Systematic review of mutations in pyrazinamidase associated with pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates. Antimicrob Agents Chemother.59:5267–5277.
  • Rawat R, Whitty A, Tonge PJ. 2003. The isoniazid-NAD adduct is a slow, tight-binding inhibitor of InhA, the Mycobacterium tuberculosis enoyl reductase: adduct affinity and drug resistance. Proc Natl Acad Sci. 100:13881–13886.
  • Rumijowska-Galewicz A, Korycka-Machała M, Lisowska K, Dziadek J. 2008. The composition of cell wall skeleton and outermost lipids of Mycobacterium vaccae is modified by ethambutol treatment. Pol J Microbiol. 57:99–104.
  • Safi H, Lingaraju S, Amin A, Kim S, Jones M, Holmes M, McNeil M, Peterson SN, Chatterjee D, Fleischmann R, Alland D. 2013. Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-d-arabinose biosynthetic and utilization pathway genes. Nat Genet. 45:1190–1197.
  • Sahu RK, Singh K, Subodh S. 2015. Adverse drug reactions to anti-TB Drugs: pharmacogenomics perspective for identification of host genetic markers. Curr Drug Metab. 16:538–552.
  • Sarkar S, Ganguly A, Sunwoo H. 2016. Current overview of anti-tuberculosis drugs: metabolism and toxicities. Mycobact Dis. 6:1–6.
  • Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, Peloquin CA, Gordin FM, Nunes D, Strader DB, et al. 2006. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 174:935–952.
  • Sayahi H, Zimhony O, Jacobs WR, Jr Shekhtman A, Welch JT. 2011. Pyrazinamide, but not pyrazinoic acid, is a competitive inhibitor of NADPH binding to Mycobacterium tuberculosis fatty acid synthase I. Bioorg Med Chem Lett.21:4804–4807.
  • Seifert M, Catanzaro D, Catanzaro A, Rodwell TC. 2015. Genetic mutations associated with isoniazid resistance in Mycobacterium tuberculosis: a systematic review. PloS One. 10:e0119628.
  • Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE, Wang H, Zhang W, Zhang Y. 2011. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 333:1630–1632.
  • Shibata K, Fukuwatari T, Sugimoto E. 2001. Effects of dietary pyrazinamide, an antituberculosis agent, on the metabolism of tryptophan to niacin and of tryptophan to serotonin in rats. Biosci Biotechnol Biochem. 65:1339–1346.
  • Starks AM, Gumusboga A, Plikaytis BB, Shinnick TM, Posey JE. 2009. Mutations at embB codon 306 are an important molecular indicator of ethambutol resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 53:1061–1066.
  • Timmins GS, Deretic V. 2006. Mechanisms of action of isoniazid. Mol Microbiol. 62:1220–1227.
  • Trupp M, Zhu H, Wikoff WR, Baillie RA, Zeng Z-B, Karp PD, Fiehn O, Krauss RM, Kaddurah-Daouk R. 2012. Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment. PLoS One. 7:e38386.
  • Unissa AN, Hanna LE. 2017. Molecular mechanism of action, resistance, detection to the first-line anti tuberculosis drugs: rifampicin and pyrazinamide. Tuberculosis. 105:96-107.
  • Unissa AN, Subbian S, Hanna LE, Selvakumar N. 2016. Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis. Infect Genet Evolut. 45:474–492.
  • Villas‐Bôas SG, Mas S, Åkesson M, Smedsgaard J, Nielsen J. 2005. Mass spectrometry in metabolome analysis. Mass Spectrom Rev. 24:613–646.
  • Wang P, Pradhan K, Zhong X-b, Ma X. 2016. Isoniazid metabolism and hepatotoxicity. Acta Pharm Sin B. 6:384–392.
  • Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S, et al. 2007. HMDB: the human metabolome database. Nucleic Acids Res. 35:D521–D526.
  • World Health Organization. 2016. WHO treatment guidelines for drug resistant tuberculosis. Geneva, Switzerland (WHO Press): World Health Organization.
  • World Health Organization. 2017a. Global tuberculosis report 2017. Geneva, Switzerland (WHO Press): World Health Organization.
  • World Health Organization. 2017b. Guidelines for treatment of drug-susceptible tuberculosis and patient care. Geneva, Switzerland (WHO Press): World Health Organization.
  • Xu Y, Jia H, Huang H, Sun Z, Zhang Z. 2015. Mutations found in embCAB, embR, and ubiA genes of ethambutol-sensitive and-resistant Mycobacterium tuberculosis clinical isolates from China. BioMed Res Int. 2015:1–8.
  • Yoshikawa Y, Hosomi H, Fukami T, Nakajima M, Yokoi T. 2009. Establishment of knockdown of superoxide dismutase 2 and expression of CYP3A4 cell system to evaluate drug-induced cytotoxicity. Toxicol in Vitro. 23:1179–1187.
  • Zenkin N, Kulbachinskiy A, Bass I, Nikiforov V. 2005. Different rifampin sensitivities of Escherichia coli and Mycobacterium tuberculosis RNA polymerases are not explained by the difference in the β-Subunit rifampin regions I and II. Antimicrob Agents Chemother. 49:1587–1590.
  • Zhang S, Chen J, Shi W, Liu W, Zhang W, Zhang Y. 2013. Mutations in panD encoding aspartate decarboxylase are associated with pyrazinamide resistance in Mycobacterium tuberculosis. Emerg Microbes Infect. 2:e34.
  • Zhang Y. 2005. The magic bullets and tuberculosis drug targets. Annu Rev Pharmacol Toxicol. 45:529–564.
  • Zhang Y, Mitchison D. 2003. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis. 7:6–21.
  • 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.
  • 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.
  • Zhang Y, Wade MM, Scorpio A, Zhang H, Sun Z. 2003. Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid. J Antimicrob Chemother. 52:790–795.
  • Zimhony O, Cox JS, Welch JT, Vilchèze C, Jacobs WR. 2000. Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 6:1043–1047.
  • Zimhony O, Vilchèze C, Arai M, Welch JT, Jacobs WR. 2007. Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother. 51:752–754.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.