Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Respiratory Research
Published in: Respiratory Research 3/2001

Open Access 01-06-2001 | Review

The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis

Authors: Akos Somoskovi, Linda M Parsons, Max Salfinger

Published in: Respiratory Research | Issue 3/2001

Login to get access

Abstract

Multidrug-resistant (MDR) strains of Mycobacterium tuberculosis have emerged worldwide. In many countries and regions, these resistant strains constitute a serious threat to the efficacy of tuberculosis control programs. An important element in gaining control of this epidemic is developing an understanding of the molecular basis of resistance to the most important antituberculosis drugs: isoniazid, rifampin, and pyrazinamide. On the basis of this information, more exacting laboratory testing, and ultimately more appropriate and timely treatment regimens, can be developed.
Literature
1.
Jarlier W, Nikaido H: Mycobacterial cell wall: structure and role in natural resistance to antibiotics. FEMS Microbiol Lett. 1994, 123: 11-18. 10.1016/0378-1097(94)90267-4.PubMedCrossRef
2.
Lee RE, Brennan PJ, Besra GS: Mycobacterium tuberculosis cell envelope. Curr Top Microbiol Immunol. 1996, 215: 1-27.PubMed
3.
Kwon HH, Tomioka H, Saito H: Distribution and characterization of beta-lactamases of mycobacteria and related organisms. Tuber Lung Dis. 1995, 76: 141-148.PubMedCrossRef
4.
Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, 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 T, Jagels K, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998, 393: 537-544. 10.1038/31159.PubMedCrossRef
5.
Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, Anderson SW, Towell JA, Yuan Y, McMurray DN, Kreiswirth BN, Barry CE, Baker WR: A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000, 405: 962-966. 10.1038/35016103.PubMedCrossRef
6.
Vester B, Douthwaite S: Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob Agents Chemother. 2001, 45: 1-12. 10.1128/AAC.45.1.1-12.2001.PubMedPubMedCentralCrossRef
7.
Heym B, Honore N, Truffot-Pernot C, Banerjee A, Schurra C, Jacobs WR, van Embden JD, Grosset JH, Cole ST: Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study. Lancet. 1994, 344: 293-298. 10.1016/S0140-6736(94)91338-2.PubMedCrossRef
8.
Zhang Y, Telenti A: Genetics of drug resistance in Mycobacterium tuberculosis. In: Molecular Genetics of Mycobacteria. Edited by Hatful GF, Jacobs WR Jr. Washington DC: ASM Press;. 2000, 235-254.
9.
World Health Organization Global Tuberculosis Programme and International Union Against Tuberculosis and Lung Disease: Anti-tuberculosis Drug Resistance in the World, Report No. 2. Prevalence and Trends. WHO/CDS/TB/2000.278. Geneva: World Health Organization;. 2000
10.
International Union Against Tuberculosis and Lung Disease: Guidelines for surveillance of drug resistance in tuberculosis. WHO Geneva/IUATLD Paris. Int J Tuberc Lung Dis. 1998, 2: 72-89.
11.
DeBarber AE, Mdluli K, Bosman M, Bekker LG, Barry CE: Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 2000, 97: 9677-9682. 10.1073/pnas.97.17.9677.PubMedPubMedCentralCrossRef
12.
Yang B, Koga H, Ohno H, Ogawa K, Fukuda M, Hirakata Y, Maesaki S, Tomono K, Tashiro T, Kohno S: Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis. J Antimicrob Chemother. 1998, 42: 621-628. 10.1093/jac/42.5.621.PubMedCrossRef
13.
Johnsson K, Schultz PG: Mechanistic studies of the oxidation of isoniazid by the catalase peroxidase from Mycobacterium tuberculosis. J Am Chem Soc. 1994, 116: 7425-7426.CrossRef
14.
Middlebrook G: Isoniazid resistance and catalase activity of tubercle bacilli. Am Rev Tuberc. 1954, 69: 471-472.PubMed
15.
Zhang Y, Heym B, Allen B, Young D, Cole S: The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature. 1992, 358: 591-593. 10.1038/358591a0.PubMedCrossRef
16.
Ramaswamy S, Musser JM: Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuberc Lung Dis. 1998, 79: 3-29. 10.1054/tuld.1998.0002.CrossRef
17.
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: 2443-2445.PubMedPubMedCentral
18.
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: 583-592. 10.1046/j.1365-2958.1996.00133.x.PubMedCrossRef
19.
Vilchèze C, Morbidoni HR, Weisbrod TR, Iwamoto H, Kuo M, Sacchettini JC, Jacobs WR: Inactivation of the inhA-encoded fatty acid synthase II (FASII) enoyl-acyl carrier protein reductase induces accumulation of the FASI end products and cell lysis of Mycobacterium smegmatis. J Bacteriol. 2000, 182: 4059-4067. 10.1128/JB.182.14.4059-4067.2000.PubMedPubMedCentralCrossRef
20.
Slayden RA, Lee RE, Barry CE: Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis. Mol Microbiol. 2000, 38: 514-525. 10.1046/j.1365-2958.2000.02145.x.PubMedCrossRef
21.
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: 2087-2089.PubMedPubMedCentral
22.
Piatek AS, Telenti A, Murray MR, El-Hajj H, Jacobs WR, 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: 103-110.PubMedPubMedCentralCrossRef
23.
Sherman DR, Mdluli K, Hickey MJ, Arain TM, Morris SL, Barry CE, Stover CK: Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis. Science. 1996, 272: 1641-1643.PubMedCrossRef
24.
Wilson T, de Lisle GW, Marcinkeviciene JA, Blanchard JS, Collins DM: Antisense RNA to ahpC, an oxidative stress defence gene involved in isoniazid resistance, indicates that AhpC of Mycobacterium bovis has virulence properties. Microbiology. 1998, 144: 2687-2695.PubMedCrossRef
25.
Mitchison DA, Nunn AJ: Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis. 1986, 133: 423-430.PubMed
26.
Grosset J: The sterilizing value of rifampicin and pyrazinamide in experimental short-course chemotherapy. Bull Int Union Tuberc. 1978, 53: 5-12.PubMed
27.
Mitchison DA: The Garrod Lecture. Understanding the chemotherapy of tuberculosis: current problems. J Antimicrob Chemother. 1992, 29: 477-493.PubMedCrossRef
28.
Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston MJ, Matter L, Schopfer K, Bodmer T: Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet. 1993, 341: 647-650. 10.1016/0140-6736(93)90417-F.PubMedCrossRef
29.
Moghazeh SL, Pan X, Arain T, Stover CK, Musser JM, Kreiswirth BN: Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations. Antimicrob Agents Chemother. 1996, 40: 2655-2657.PubMedPubMedCentral
30.
Ohno H, Koga H, Kohno S, Tashiro T, Hara K: Relationship between rifampin MICs for and rpoB mutations of Mycobacterium tuberculosis strains isolated in Japan. Antimicrob Agents Chemother. 1996, 40: 1053-1056.PubMedPubMedCentral
31.
Heep M, Rieger U, Beck D, Lehn N: Mutations in the beginning of the rpoB gene can induce resistance to rifamycins in both Helicobacter pylori and Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2000, 44: 1075-1077. 10.1128/AAC.44.4.1075-1077.2000.PubMedPubMedCentralCrossRef
32.
Zimhony O, Cox JS, Welch JT, Vilcheze C, Jacobs WR: Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nature Med. 2000, 6: 1043-1047. 10.1038/79558.PubMedCrossRef
33.
Salfinger M, Crowle AJ, Reller LB: Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system. J Infect Dis. 1990, 162: 201-207.PubMedCrossRef
34.
Zhang Y, Scorpio A, Nikaido H, Sun Z: Role of acid pH and deficient efflux of pyrazinoic acid in unique susceptibility of Mycobacterium tuberculosis to pyrazinamide. J Bacteriol. 1999, 181: 2044-2049.PubMedPubMedCentral
35.
Konno K, Feldman FM, McDermont W: Pyrazinamide susceptibility and amidase activity of the tubercle bacilli. Am Rev Respir Dis. 1967, 95: 461-469.PubMed
36.
Scorpio A, Zhang Y: Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the anti-tuberculous drug pyrazinamide in tubercle bacillus. Nature Med. 1996, 2: 662-667.PubMedCrossRef
37.
Raynaud C, Laneelle MA, Senaratne RH, Draper P, Laneelle G, Daffe M: Mechanisms of pyrazinamide resistance in mycobacteria: importance of lack of uptake in addition to lack of pyrazinamidase activity. Microbiology. 1999, 145: 1359-1367.PubMedCrossRef
38.
Van Rie A, Warren R, Mshanga I, Jordaan AM, van der Spuy GD, Richardson M, Simpson J, Gie RP, Enarson DA, Beyers N, van Helden PD, Victor TC: Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community. J Clin Microbiol. 2001, 39: 636-641. 10.1128/JCM.39.2.636-641.2001.PubMedPubMedCentralCrossRef
39.
Hale YM, Desmond EP, Jost KC, Salfinger M: Access to newer laboratory procedures: a call for action. Int J Tuberc Lung Dis. 2000, 4(suppl 2): S171-S175.
40.
Parsons LM, Driscoll JR, Taber HW, Salfinger M: Drug resistance in tuberculosis. Infect Dis Clin North Am. 1997, 11: 905-928.PubMedCrossRef
Metadata
Title
The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis
Authors
Akos Somoskovi
Linda M Parsons
Max Salfinger
Publication date
01-06-2001
Publisher
BioMed Central
Published in
Respiratory Research / Issue 3/2001
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/rr54

Other articles of this Issue 3/2001

Respiratory Research 3/2001 Go to the issue

Review

Modulation of pulmonary vasomotor tone in the fetus and neonate

Review

Recent advances in our understanding of human host responses to tuberculosis

Review

The heterotopic tracheal allograft as an animal model of obliterative bronchiolitis

Research

Recurrent pneumonia with mild hypogammaglobulinemia diagnosed as X-linked agammaglobulinemia in adults

Commentary

Immunologists getting nervous: neuropeptides, dendritic cells and T cell activation

Review

Eotaxin and the attraction of eosinophils to the asthmatic lung
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits