Resistencia a Medicamentos en Mycobacterium tuberculosis: contribución de mecanismos constitutivos y adquiridos
Drug resistance in Mycobacterium tuberculosis: contribution of constituent and acquired mechanisms
DOI:
https://doi.org/10.15446/rsap.v20n4.50575Palabras clave:
Resistencia a medicamentos, mycobacterium tuberculosis, tuberculosis resistente a múltiples medicamentos (es)Drug resistance, mycobacterium tuberculosis, tuberculosis, multidrug resistant (en)
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Due to the emergence of multi-drug resistant (MDR-MTB) and extensively drug-resistant (XDR-MTB) Mycobacterium tuberculosis (MTB) isolates, the failure rates of standard treatment regimens are high, thus becoming a major public health challenge worldwide. Resistance to anti-tuberculous (anti-TB) drugs is attributed mainly to specific mutations in target genes; however, a proportion of drug-resistant MTB isolates do not have mutations in these genes, which suggests the involvement of other mechanisms, such as the low permeability of the mycobacterial cell wall, enzymatic modification and/or efflux pumps.
Clinical drug resistance to anti-TB drugs occurs largely as a result of the selection of resistant mutants caused by poor patient adherence to treatment, inappropriate follow-ups and prescriptions, suboptimal doses of drugs and poor access to health services and treatment. Major advances in molecular biology tools and the availability of the complete genome sequences of MTB have contributed to improve understanding of the mechanisms of resistance to the main anti-TB drugs. Better knowledge of the drug-resistance of MTB will contribute to the identification of new therapeutic targets to design new drugs, develop new diagnostic tests and/or improve methods currently available for the rapid detection of drug-resistant TB. This article presents an updated review of the mechanisms and molecular basis of drug resistance in MTB.
Referencias
Chiang C-Y, Centis R, Migliori GB. Drug-resistant tuberculosis: past, present, future. Respirol Carlton Vic. 2010 Apr;15(3):413–32.
Frieden TR, Sterling TR, Munsiff SS, Watt CJ, Dye C. Tuberculosis. Lancet. 2003 Sep 13;362(9387):887–99.
World Health Organization. Global tuberculosis control 2008: surveillance, planning, financing. Geneva: WHO; 2008.
World Health Organization: Global tuberculosis report 2016. Geneva: WHO; 2016.
Organización Panamericana de la Salud, Instituto Nacional de Salud, Ministerio de la Protección Social (Colombia). Esquemas de tratamiento para tuberculosis en Colombia. Bogotá: OPS; 2007.
World Health Organization. Treatment of tuberculosis: guidelines. 4. ed. Geneva, Switzerland: WHO; 2009.
Wade MM, Zhang Y. Mechanisms of drug resistance in Mycobacterium tuberculosis. Front Biosci J Virtual Libr. 2004 Jan 1;9:975–94.
Dorman SE, Chaisson RE. From magic bullets back to the magic mountain: the rise of extensively drug-resistant tuberculosis. Nat Med. 2007 Mar;13(3):295–8.
Iseman MD. Evolution of drug-resistant tuberculosis: a tale of two species. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2428–9.
World Health Organization. Drug-Resistant TB Surveillance & Response. WHO/HQ/TB/2014.
Malik S, Willby M, Sikes D, Tsodikov OV, Posey JE. New insights into fluoroquinolone resistance in Mycobacterium tuberculosis: functional genetic analysis of gyrA and gyrB mutations. PloS One. 2012;7(6):e39754.
World Health Organization. Anti-tuberculosis Drug resistance in the world report 4. Geneva: WHO; 2008.
Instituto Nacional de Salud. Subdirección de Vigilancia y Control de Salud Pública. Cumplimiento en la notificación, semana epidemiológica 52. Boletín Epidemiológico Semanal. 2014 Dic 21-27(52):1-28.
Gomez IT, Llerena CR, Zabaleta AP. Tuberculosis y tuberculosis farmacorresistente en personas privadas de la libertad. Colombia, 2010-2012. Rev. Salud Pública. 17(1): 97-105, 2015
Garzón MC, Angée DY, Llerena C, Orjuela DL, Victoria JE. Vigilancia de la resistencia del Mycobacterium tuberculosis a los fármacos antituberculosos, Colombia 2004-2005. Biomédica. 2008 Sep 1;28(3):319–26.
Instituto Nacional de Salud. Protocolo de vigilancia en salud pública: Tuberculosis fármacoresistente. Colombia. INS; 2014.
Brudney K, Dobkin J. Resurgent tuberculosis in New York City. Human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs. Am Rev Respir Dis. 1991 Oct;144(4):745–9.
Palomino JC. Nonconventional and new methods in the diagnosis of tuberculosis: feasibility and applicability in the field. Eur Respir J. 2005 Aug; 26(2):339–50.
Hernández Sarmiento JM, Martínez Negrete MA, Castrillon Velilla Diana M, Mejia Espinosa Sergio A, Mejia Mesa GI. Zapate Fernández EM. et al. Agar de capa delgada: Una opción costo-efectiva para el diagnóstico rápido de tuberculosis multirresistente. Rev. Salud Pública. (Bogotá). 2014; 16(1):101-113.
Fajardo A, Martínez-Martín N, Mercadillo M, Galán JC, Ghysels B, Matthijs S, et al. The neglected intrinsic resistome of bacterial pathogens. PloS One. 2008; 3(2):e1619.
Giedraitienė A, Vitkauskienė A, Naginienė R, Pavilonis A. Antibiotic resistance mechanisms of clinically important bacteria. Med Kaunas Lith. 2011; 47(3):137-46.
Jalal KCA, Akbar B, Kamaruzzaman BY, Kathires K. Emergence of Antibiotic Resistant Bacteria from Coastal Environment - A Review. In: Pana M, editor. Antibiotic Resistant Bacteria - A Continuous Challenge in the New Millennium [Internet]. Hampshire, England: InTech; 2012 [cited 2014 Jun 23]. Available from:http://www.intechopen.com/books/howtoreference/antibiotic-resistant-bacteria-a-continuous-challenge-in-the-new-millennium/emergence- of-antibiotic-resistant-bacteria-from-coastal-environment-a-review.
Jarlier V, Nikaido H. Mycobacterial cell wall: structure and role in natural resistance to antibiotics. FEMS Microbiol Lett. 1994 Oct 15; 123(1-2):11–8.
Nguyen L, Thompson CJ. Foundations of antibiotic resistance in bacterial physiology: the mycobacterial paradigm. Trends Microbiol. 2006 Jul; 14(7):304–12.
Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H. Mycobacterial outer membranes: in search of proteins. Trends Microbiol. 2010 Mar; 18(3):109–16.
Brennan PJ, Nikaido H. The envelope of mycobacteria. Annu Rev Biochem.1995; 64:29–63.
Niederweis M. Mycobacterial porins--new channel proteins in unique outer membranes. Mol Microbiol. 2003 Sep; 49(5):1167–77.
Wright GD. Bacterial resistance to antibiotics: enzymatic degradation and modification. Adv Drug Deliv Rev. 2005 Jul 29; 57(10):1451–70.
Buriánková K, Doucet-Populaire F, Dorson O, Gondran A, Ghnassia J-C, Weiser J, et al. Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex. Antimicrob Agents Chemother. 2004 Jan; 48(1):143–50.
Madsen CT, Jakobsen L, Buriánková K, Doucet-Populaire F, Pernodet J-L, Douthwaite S. Methyltransferase Erm(37) slips on rRNA to confer atypical resistance in Mycobacterium tuberculosis. J Biol Chem. 2005 Nov 25; 280(47):38942–7.
Akbergenov R, Shcherbakov D, Matt T, Duscha S, Meyer M, Wilson DN, et al. Molecular basis for the selectivity of antituberculosis compounds capreomycin and viomycin. Antimicrob Agents Chemother. 2011 Oct;55(10):4712–7.
Maus CE, Plikaytis BB, Shinnick TM. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2005 Feb; 49(2):571–7.
Johansen SK, Maus CE, Plikaytis BB, Douthwaite S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2’-O- methylations in 16S and 23S rRNAs. Mol Cell. 2006 Jul 21;23(2):173–82.
Chambers HF, Moreau D, Yajko D, Miick C, Wagner C, Hackbarth C, et al. Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis? Antimicrob Agents Chemother. 1995 Dec;39(12):2620–4.
Voladri RK, Lakey DL, Hennigan SH, Menzies BE, Edwards KM, Kernodle DS. Recombinant expression and characterization of the major beta-lactamase of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1998 Jun;42(6):1375–81.
Wang F, Cassidy C, Sacchettini JC. Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics. Antimicrob Agents Chemother. 2006 Aug;50(8):2762–71.
Flores AR, Parsons LM, Pavelka MS. Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics. Microbiol Read Engl. 2005 Feb;151(Pt 2):521–32.
Louw GE, Warren RM, Gey van Pittius NC, McEvoy CRE, Van Helden PD, Victor TC. A balancing act: efflux/influx in mycobacterial drug resistance. Antimicrob Agents Chemother. 2009 Aug;53(8):3181–9.
Piddock LJV. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev. 2006 Apr; 19(2):382–402.
Kumar A, Schweizer HP. Bacterial resistance to antibiotics: active efflux and reduced uptake. Adv Drug Deliv Rev. 2005 Jul 29;57(10):1486–513.
Marquez B. Bacterial efflux systems and efflux pumps inhibitors. Biochimie. 2005 Dec; 87(12):1137–47.
Gupta AK, Katoch VM, Chauhan DS, Sharma R, Singh M, Venkatesan K, et al. Microarray analysis of efflux pump genes in multidrug-resistant Mycobacterium tuberculosis during stress induced by common anti-tuberculous drugs. Microb Drug Resist Larchmt N. 2010 Mar;16(1):21–8.
Ramaswamy S, Musser JM. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber Lung Dis Off J Int Union Tuberc Lung Dis. 1998; 79(1):3–29.
Ramaswamy SV, Reich R, Dou S-J, Jasperse L, Pan X, Wanger A, et al. Single nucleotide polymorphisms in genes associated with isoniazid resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2003 Apr; 47(4):1241–50.
Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston MJ, et al. Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet. 1993 Mar 13; 341(8846):647–50.
Rees DC, Johnson E, Lewinson O. ABC transporters: the power to change. Nat Rev Mol Cell Biol. 2009 Mar; 10(3):218–27.
Nikaido H, Zgurskaya HI. Antibiotic efflux mechanisms. Curr Opin Infect Dis. 1999 Dec; 12(6):529–36.
Müller B, Borrell S, Rose G, Gagneux S. The heterogeneous evolution of multidrug-resistant Mycobacterium tuberculosis. Trends Genet TIG. 2013 Mar; 29(3):160–9.
Araya P, Velasco M, Tognarelli J, Arias F, Leiva T, Sccapatticio A, et al. [Detection of genes associated with drug resistance in Mycobacterium tuberculosis strains isolated in Chile]. Rev Médica Chile. 2011 Apr; 139(4):467–73.
Borrell S, Gagneux S. Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis. 2009 Dec; 13(12):1456–66.
De Steenwinkel JEM, ten Kate MT, de Knegt GJ, Kremer K, Aarnoutse RE, Boeree MJ, et al. Drug susceptibility of Mycobacterium tuberculosis Beijing genotype and association with MDR TB. Emerg Infect Dis. 2012 Apr; 18(4):660–3.
Baranov AA, Mariandyshev AO, Mannsåker T, Dahle UR, Bjune GA. Molecular epidemiology and drug resistance of widespread genotypes of Mycobacterium tuberculosis in northwestern Russia. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis. 2009 Oct; 13(10):1288–93.
Kubica T, Agzamova R, Wright A, Aziz MA, Rakishev G, Bismilda V, et al. The Beijing genotype is a major cause of drug-resistant tuberculosis in Kazakhstan. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis. 2005 Jun; 9(6):646–53.
Acevedo GA, Vega A, Ribón W. Tuberculosis Multidrogoresistente. rev.univ.ind.santander.salud. 2013 Sep; 45(3):87–92.
Shoeb HA, Bowman BU, Ottolenghi AC, Merola AJ. Peroxidase-mediated oxidation of isoniazid. Antimicrob Agents Chemother. 1985 Mar; 27(3):399–403.
Youatt J. A review of the action of isoniazid. Am Rev Respir Dis. 1969 May; 99(5):729–49.
Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science. 1994 Jan 14; 263(5144):227–30.
Rawat R, Whitty A, Tonge PJ. 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 U S A. 2003 Nov 25; 100(24):13881–6.
Heym B, Stavropoulos E, Honoré N, Domenech P, Saint-Joanis B, Wilson TM, et al. Effects of overexpression of the alkyl hydroperoxide reductase AhpC on the virulence and isoniazid resistance of Mycobacterium tuberculosis. Infect Immun. 1997 Apr; 65(4):1395–401.
Lee AS, Teo AS, Wong SY. Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother. 2001 Jul; 45(7):2157–9.
Slayden RA, Barry CE. The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis. Tuberc Edinb Scotl. 2002; 82(4-5):149–60.
Hazbón MH, Brimacombe M, Bobadilla del Valle M, Cavatore M, Guerrero MI, Varma-Basil M, et al. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2006 Aug; 50(8):2640–9.
Vareldzis BP, Grosset J, de Kantor I, Crofton J, Laszlo A, Felten M, et al. Drug-resistant tuberculosis: laboratory issues. World Health Organization recommendations. Tuber Lung Dis Off J Int Union Tuberc Lung Dis. 1994 Feb; 75(1):1–7.
Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, et al. Structural mechanism for rifampicin inhibition of bacterial rna polymerase. Cell. 2001 Mar 23; 104(6):901–12.
Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med. 1993 Sep 9; 329(11):784–91.
Berning SE. The role of fluoroquinolones in tuberculosis today. Drugs. 2001; 61(1):9–18.
Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003 Feb 15; 167(4):603–62.
Hawkey PM. Mechanisms of quinolone action and microbial response. J Antimicrob Chemother. 2003 May;51 Suppl 1:29–35.
Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11; 393(6685):537–44.
World Health Organization. Global tuberculosis control-epidemiology, strategy, financing. World Report. Geneva, Switzerland: WHO; 2009.
Almeida Da Silva PEA, Palomino JC. Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs. J Antimicrob Chemother. 2011 Jul; 66(7):1417–30.
Alangaden GJ, Kreiswirth BN, Aouad A, Khetarpal M, Igno FR, Moghazeh SL, et al. Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother.1998 May; 42(5):1295–7.
Maus CE, Plikaytis BB, Shinnick TM. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2005 Aug; 49(8):3192–7.
Via LE, Cho S-N, Hwang S, Bang H, Park SK, Kang HS, et al. Polymorphisms associated with resistance and cross-resistance to aminoglycosides and capreomycin in Mycobacterium tuberculosis isolates from South Korean Patients with drug-resistant tuberculosis. J Clin Microbiol. 2010 Feb; 48(2):402–11.
Musser JM. Antimicrobial agent resistance in mycobacteria: molecular genetic insights. Clin Microbiol Rev. 1995 Oct; 8(4):496–514.
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