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Narrative Review

Vol. 6 No. 2 (2002)

Isoniazid, The Frontline of Resistance in Mycobacterium tuberculosis

  • James B. Whitney B.Sc.
  • Mark A. Wainberg Ph.D.
DOI
https://doi.org/10.26443/mjm.v6i2.686
Submitted
November 8, 2020
Published
2002-12-01

Abstract

Tuberculosis is an ancient disease that has held close association with humans for millennia. Through persistence, this remarkably successful organism has managed to infect an estimated third of the world's population. Declining rates of tuberculosis in developed nations have masked an emerging epidemic of drug resistant cases that have been reported in almost every country under scrutiny. The recent completion of the genome sequence of Mycobacterium tuberculosis has mandated more efficient control and management of this disease. The momentum for this public health imperative will come from information gleaned from advances in genomics and related technologies towards deciphering molecular mechanisms of mycobacterial drug resistance.

References

  1. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project JAMA. 1999; 282(7): 677- 86.
  2. Dolin P.J., Raviglione M.C. and Kochi A., Global tuberculosis incedence and mortality during 1990-2000. Bull WHO 72: 213- 220.
  3. Harrison's Principles of Internal Medicine 15th edition, vol1 pgs 1024-1033. 2000.
  4. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med; 2001 345(3): 189-200.
  5. Mahmoudi A, Iseman MD. Pitfalls in the care of patients with tuberculosis. Common errors and their association with the acquisition of drug resistance. JAMA. 1993; 270(1): 65-8.
  6. Moss AR, Hahn JA, Tulsky JP, Daley CL, Small PM, Hopewell PC. Tuberculosis in the homeless. A prospective study. Am J Respir Crit Care Med. 2000;162( 2 Pt 1): 460-4.
  7. Prospects for vaccines to protect against AIDS, tuberculosis, and malaria. Letvin NL, Bloom BR, Hoffman SL. JAMA. 2001; 285(5): 606-11.
  8. Tuberculosis and HIV infection in sub-Saharan Africa. De Cock KM, Soro B, Coulibaly IM, Lucas SB. JAMA. 1992; 268(12): 1581-71.
  9. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby, Jagels K, Barrell BG. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence Nature. 1998; 393(6685): 537-44.
  10. Philipp WJ, Poulet S, Eiglmeier K, Pascopella L, Balasubramanian V, Heym B, Bergh S, Bloom BR, Jacobs WR Jr, Cole ST. An integrated map of the genome of the tubercle bacillus, Mycobacterium tuberculosis H37Rv, and comparison with Mycobacterium leprae Proc Natl Acad Sci U S A. 1996; 93(7): 3132-7.
  11. Sterling TR, Brehm WT, Moore RD, Chaisson RE. Tuberculosis vaccination versus isoniazid preventive therapy: a decision analysis to determine the preferred strategy of tuberculosis prevention in HIV- infected adults in the developing world. Int J Tuberc Lung Dis. 1999; 3(3): 248-54.
  12. Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic JAMA. 1999; 281(11): 1014-8.
  13. Gurumurthy P, Ramachandran G, Vijayalakshmi S, Kumar AK, Venkatesan P, Chandrasekaran V, Vjayasekaran V Kumaraswami V, Prabhakar R. Bioavailability of rifampicin, isoniazid and pyrazinamide in a triple drug formulation: comparison of plasma and urine kinetics. Int J Tuberc Lung Dis. 1999; 3(2): 119-25.
  14. Bass JB Jr, Farer LS, Hopewell PC, O'Brien R, Jacobs RF, Ruben F, Snider DE Jr, Thornton G. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J Respir Crit Care Med. 1994; 149(5):1359-74.
  15. Bardou F, Raynaud C, Ramos C, Laneelle MA, Laneelle G. Mechanism of isoniazid uptake in Mycobacterium tuberculosis. Microbiology. 1998; 144 (9): 2539-44.
  16. Musser JM. Antimicrobial agent resistance in mycobacteria: molecular genetic insights. Clin Microbiol Rev. 1995; 8(4): 496-514.
  17. Middlebrook G. Isoniazid-resistance and catalase activity of tubercle bacilli Am Rev Tuberc. 1954; 69:471-472.
  18. Loewen P.C. Klotz MG, Hassett DJ, an old enzyme that continues to surprise us. ASM News. 2000; 66:76-82.
  19. Li Z, Kelley C, Collins F, Rouse D, Morris S. Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs. J Infect Dis. 1998; 177(4): 1030- 5.
  20. Shoeb HA, Bowman BU Jr, Ottolenghi AC, Merola AJ. Peroxidase- mediated oxidation of isoniazid. Antimicrob Agents Chemother. 1985; 27(3): 399-403.
  21. Shoeb HA, Bowman BU Jr, Ottolenghi AC, Merola AJ. Evidence for the generation of active oxygen by isoniazid treatment of extracts of Mycobacterium tuberculosis H37Ra. Antimicrob Agents Chemother. 1985; 27(3):404-7.
  22. Zhang Y, Heym B, Allen B, Young D, Cole S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature. 1992; 358(6387): 591-3.
  23. Nikaido H. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science. 1994; 264(5157): 382-8.
  24. Spratt BG. Resistance to antibiotics mediated by target alterations Science. 1994; 264(5157): 388-93.
  25. Davies J. Inactivation of antibiotics and the dissemination of resistance genes. Science. 1994; 64(5157): 375-82.
  26. Heym B, Alzari PM, Honore N, Cole ST Missense mutations in the catalase-peroxidase gene, katG, are associated with isoniazid resistance in Mycobacterium tuberculosis Mol Microbiol. 1995;15(2): 235-45.
  27. Cockerill FR 3rd. Genetic methods for assessing antimicrobial resistance. Antimicrob Agents Chemother. 1999; 43 (2): 199-212.
  28. Olive M.D., Bean P. Principles and applications of methods for DNA- based typing of microbial organisms. J Clin Micro. 1999; 37(6): 1661-1669.
  29. Pretorius GS, van Helden PD, Sirgel F, Eisenach KD, Victor TC. Mutations in katG gene sequences in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis are rare. Antimicrob Agents Chemother. 1995; 39(10): 2276-81.
  30. Marttila HJ, Soini H, Eerola E, Vyshnevskaya E, Vyshnevskiy BI, Otten TF, Vasilyef AV, Viljanen MK. A Ser315Thr substitution in KatG is predominant in genetically heterogeneous multidrug-resistant Mycobacterium tuberculosis isolates originating from the St. Petersburg area in Russia. Antimicrob Agents Chemother. 1998; 42(9): 2443-5.
  31. Marttila HJ, Soini H, Huovinen P, Viljanen MK. katG mutations in isoniazid-resistant Mycobacterium tuberculosis isolates recovered from Finnish patients. Antimicrob Agents Chemother. 1996; 40(9): 2187-9.
  32. van Soolingen D, de Haas PE, van Doorn HR, Kuijper E, Rinder H, Borgdorff MW. Mutations at Amino Acid Position 315 of the katG Gene Are Associated with High-Level Resistance to Isoniazid, Other Drug Resistance, and Successful Transmission of Mycobacterium tuberculosis in The Netherlands. J Infect Dis 2000; 182(6):1788-1790.
  33. Rouse DA, Li Z, Bai GH, Morris SL. Characterization of the katG and inhA genes of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1995; 39(11):2472-7.
  34. Haas WH, Schilke K, Brand J, Amthor B, Weyer K, Fourie PB, Bretzel G, Sticht-Groh V, Bremer HJ. Molecular analysis of katG gene mutations in strains of Mycobacterium tuberculosis complex from Africa. Antimicrob Agents Chemother. 1997; 41(7): 1601-3.
  35. Musser JM, Kapur V, Williams DL, Kreiswirth BN, van Soolingen D, van Embden JD. Characterization of the catalase-peroxidase gene (katG) and inhA locus in isoniazid-resistant and -susceptible strains of Mycobacterium tuberculosis by automated DNA sequencing: restricted array of mutations associated with drug resistance. J Infect Dis. 1996; 173(1):196-202.
  36. Rouse DA, DeVito JA, Li Z, Byer H, Morris SL Site-directed mutagenesis of the katG gene of Mycobacterium tuberculosis: effects on catalase-peroxidase activities and isoniazid resistance. Mol Microbiol. 1996; 22(3): 583-92.
  37. Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, Small PM.. Comparative genomics of BCG vaccines by whole- genome DNA microarray. Science. 1999; 284(5419): 1520-3.
  38. Behr MA, Small PM. A historical and molecular phylogeny of BCG strains. Vaccine; 1999; 17(7-8): 915-22.
  39. Wengenack NL, Todorovic S, Yu L, Rusnak F. Evidence for differential binding of isoniazid by Mycobacterium tuberculosis KatG and the isoniazid-resistant mutant KatG (S315T). Biochemistry. 1998; 37(45): 15825-34.
  40. Johnsson K, Froland WA, Schultz PG. Overexpression, purification, and characterization of the catalase-peroxidase KatG from Mycobacterium tuberculosis J Biol Chem. 1997; 272(5): 2834-40.
  41. Van Doorn HR, Kuijper EJ, van Der Ende A, Welten AG, van Soolingen D, de Haas PE, Dankert J The Susceptibility of Mycobacterium tuberculosis to Isoniazid and the Arg-->Leu Mutation at Codon 463 of katG Are Not Associated. J Clin Microbiol. 2001; 39(4): 1591-4.
  42. Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, de Lisle G, Jacobs WR Jr. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science. 1994; 263(5144): 227-30.
  43. Dessen A, Quemard A, Blanchard JS, Jacobs WR Jr, Sacchettini JC. Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Science. 1995; 267(5204): 1638-41.
  44. Rozwarski DA, Grant GA, Barton DHR, Jacobs WR Jr, Sacchettini JC. Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science. 1998; 279(5347): 98-102.
  45. Lei B, Wei CJ, Tu SC. Action mechanism of antitubercular isoniazid. Activation by Mycobacterium tuberculosis KatG, isolation, and characterization of inhA inhibitor J Biol Chem. 2000; 275(4): 2520-6.
  46. Mdluli K, Sherman DR, Hickey MJ, Kreiswirth BN, Morris S, Stover CK, Barry CE 3rd. Biochemical and genetic data suggest that InhA is not the primary target for activated isoniazid in Mycobacterium tuberculosis. J Infect Dis. 1996; 174(5): 1085-90.
  47. Mdluli K, Slayden RA, Zhu Y, Ramaswamy S, Pan X, Mead D, Crane DD, Musser JM, Barry CE 3rd. Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid. Science. 1998; 280(5369): 1607-10.
  48. Lee AS, Lim IH, Tang LL, Telenti A, Wong SY. Contribution of kasA analysis to detection of isoniazid-resistant Mycobacterium tuberculosis in Singapore. Antimicrob Agents Chemother. 1999; 43(8): 2087-9.
  49. Slayden RA, Lee RE, Barry CE 3rd. Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis. Mol Microbiol. 2000; 38(3): 514-25.
  50. Sherman DR, Sabo PJ, Hickey MJ, Arain TM, Mahairas GG, Yuan Y, Barry CE 3rd, Stover CK. Disparate responses to oxidative stress in saprophytic and pathogenic mycobacteria. Proc Natl Aced Sci U S A . 1995; 92(14): 6625-9.
  51. Deretic V, Philipp W, Dhandayuthapani S, Mudd MH, Curcic R, Garbe T, Heym B, Via LE, Cole ST. Mycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid. Mol. Microbiol. 1995; 17(5): 889-900.
  52. Dhandayuthapani S, Mudd M, Deretic V. Interactions of OxyR with the promoter region of the oxyR and ahpC genes from Mycobacterium leprae and Mycobacterium tuberculosis. J Bacteriol. 1997; 179(7):2401-9.
  53. Sherman DR, Mdluli K, Hickey MJ, Arain TM, Morris SL, Barry CE 3rd, Stover CK. Compensatory ahpC gene expression in isoniazid- resistant Mycobacterium tuberculosis. Science. 1996; 272(5268): 1641-3.
  54. Zhang Y, Dhandayuthapani S, Deretic V. Molecular basis for the exquisite sensitivity of Mycobacterium tuberculosis to isoniazid Proc Natl Acad Sci U S A. 1996; 93(23): 13212-6.
  55. Rosner JL, Storz G. Effects of peroxides on susceptibilities of Escherichia coli and Mycobacterium smegmatis to isoniazid. Antimicrob Agents Chemother. 1994; 38(8): 1829-33.
  56. Sreevatsan S, Pan X, Zhang Y, Deretic V, Musser JM. Analysis of the oxyR-ahpC region in isoniazid-resistant and -susceptible Mycobacterium tuberculosis complex organisms recovered from diseased humans and animals in diverse localities Antimicrob Agents Chemother. 1997; 41(3): 600-6.
  57. Kelley CL, Rouse DA, Morris SL. Analysis of ahpC gene mutations in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis Antimicrob Agents Chemother. 1997; 41(9): 2057-8.
  58. Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM Expression profiling using cDNA microarrays. Nat Genet. 1999; 21(1 Suppl): 10-4.
  59. Arigoni F, Talabot F, Peitsch M, Edgerton MD, Meldrum E, Allet E, Fish R, Jamotte T, Curchod ML, Loferer H A genome-based approach for the identification of essential bacterial genes. Nat Biotechnol. 1998; 16(9): 851-6.
  60. Lennon GG. High-throughput gene expression analysis for drug discovery Drug Discov Today. 2000; 5(2): 59-66.
  61. Moir DT, Shaw KJ, Hare RS, Vovis GF. Genomics and antimicrobial drug discovery. Antimicrob Agents Chemother. 1999; 43(3): 439-46.
  62. Debouck C, Goodfellow PN. DNA microarrays in drug discovery and development Nat Genet. 1999; 21(1 Suppl):48-50.
  63. Rosamond J, Allsop A. Harnessing the power of the genome in the search for new antibiotics. Science. 2000; 287(5460): 1973-6.
  64. Lipshutz RJ, Fodor SP, Gingeras TR, Lockhart DJ. High density synthetic oligonucleotide arrays. Nat Genet. 1999; 21(1 Suppl): 20-4.
  65. Brent R. Genomic biology Cell. 2000; 100(1): 169-83.
  66. Wilson M, DeRisi J, Kristensen HH, Imboden P, Rane S, Brown PO, Schoolnik GK. Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization Proc Natl Acad Sci U S A. 1999; 96(22): 12833-8.
  67. Garbe TR, Hibler NS, Deretic V. Isoniazid induces expression of the antigen 85 complex in Mycobacterium tuberculosis Antimicrob Agents Chemother. 1996; 40(7):1754-6.
  68. Ronning DR, Klabunde T, Besra GS, Vissa VD, Belisle JT, Sacchettini JC. Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines. Nat Struct Biol. 2000; 7(2): 141-6.
  69. Alland D, Kramnik I, Weisbrod TR, Otsubo L, Cerny R, Miller LP, Jacobs WR Jr, Bloom BR. Identification of differentially expressed mRNA in prokaryotic organisms by customized amplification libraries (DECAL): the effect of isoniazid on gene expression in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1998; 95(22): 13227-32.
  70. Brenner S, Williams SR, Vermaas EH, Storck T, Moon K, McCollum C, Mao JI, Luo S, Kirchner JJ, Eletr S, DuBridge RB, Burcham T, Albrecht G. In vitro cloning of complex mixtures of DNA on microbeads: physical separation of differentially expressed cDNAs Proc Natl Acad Sci U S A. 2000; 97(4): 1665-70.
  71. Alland D, Steyn AJ, Weisbrod T, Aldrich K, Jacobs WR Jr. Characterization of the Mycobacterium tuberculosis iniBAC promoter, a promoter that responds to cell wall biosynthesis inhibition. J Bacteriol. 2000; 182(7): 1802-11.
  72. Piatek AS, Telenti A, Murray MR, El-Hajj H, Jacobs WR Jr, Kramer FR, Alland D.Genotypic analysis of Mycobacterium tuberculosis in two distinct populations using molecular beacons: implications for rapid susceptibility testing Antimicrob Agents Chemother. 2000; 44(1):103-10.
  73. Tyagi S, Marras SA, Kramer FR. Wavelength-shifting molecular beacons. Nat Biotechnol. 2000; 18(11): 1191-6.
  74. Slayden RA, Barry CE 3rd The genetics and biochemistry of isoniazid resisitance in Mycobacterium tuberculosis. Microbes Infect 2000; 2(6): 659-69.

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