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REVIEW ARTICLE

Fighting an old disease with modern tools: characteristics and molecular detection methods of drug-resistant Mycobacterium tuberculosis

Pages 1-17 | Received 22 Apr 2015, Accepted 03 Jun 2015, Published online: 13 Jul 2015

References

  • Comas I, Coscolla M, Luo T, Borrell S, Holt KE, Kato-Maeda M, et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet 2013;45:1176–82.
  • World Health Organization. Global report on tuberculosis 2014. WHO; 2014.
  • 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;282:677–86.
  • Comstock GW. Epidemiology of tuberculosis. Am Rev Respir Dis 1982;125:8–15.
  • Aaron L, Saadoun D, Calatroni I, Launay O, Memain N, Vincent V, et al. Tuberculosis in HIV-infected patients: a comprehensive review. Clin Microbiol Infect 2004;10: 388–98.
  • Andersen P, Doherty TM. The success and failure of BCG – implications for a novel tuberculosis vaccine. Nat Rev Microbiol 2005;3:656–62.
  • World Health Organization. Treatment of tuberculosis: guidelines, 4th edn. WHO; 2010.
  • Gandhi NR, Nunn P, Dheda K, Schaaf HS, Zignol M, van Soolingen D, et al. Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet 2010;375:1830–43.
  • Tiemersma EW, van der Werf MJ, Borgdorff MW, Williams BG, Nagelkerke NJ. Natural history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative patients: a systematic review. PLoS One 2011;6:e17601.
  • Dheda K, Migliori GB. The global rise of extensively drug-resistant tuberculosis: is the time to bring back sanatoria now overdue? Lancet 2012;379:773–5.
  • Lewis K. Platforms for antibiotic discovery. Nat Rev Drug Discov 2013;12:371–87.
  • Youmans GP, Williston EH, et al. Increase in resistance of tubercle bacilli to streptomycin; a preliminary report. Proc Staff Meet Mayo Clin 1946;21:126.
  • Lehmann J. Para-aminosalicylic acid in the treatment of tuberculosis. Lancet 1946;1:15.
  • Bernstein J, Lott WA, Steinberg BA, Yale HL. Chemotherapy of experimental tuberculosis. V. Isonicotinic acid hydrazide (nydrazid) and related compounds. Am Rev Tuberc 1952; 65:357–64.
  • Canetti G, Rist N, Grosset J. Primary drug resistance in tuberculosis. Am Rev Respir Dis 1964;90:792–9.
  • Horne NW. Drug-resistant tuberculosis: a review of the world situation. Tubercle 1969;50(Suppl):2–12.
  • Cole ST, Eisenach KD, McMurray DN, Jacobs WRJ, editors. Tuberculosis and the tubercle bacillus. ASM Press; 2004.
  • Rist N, Crofton J. Drug resistance in hospitals and sanatoria. A report to the committee on laboratory methods and to the committee on antibiotics and chemotherapy of the International Union against Tuberculosis. Bull Int Union Tuberc 1960;30:3–39.
  • Waksman SA. The conquest of tuberculosis. Robert Hale Ltd; 1964.
  • Thomas JP, Baughn CO, Wilkinson RG, Shepherd RG. A new synthetic compound with antituberculous activity in mice: ethambutol (dextro-2,2’-(ethylenediimino)-di-l-butanol). Am Rev Respir Dis 1961;83:891–3.
  • Iseman MD. Tuberculosis therapy: past, present and future. Eur Respir J Suppl 2002;36:87s–94s.
  • Maggi N, Pasqualucci CR, Ballotta R, Sensi P. Rifampicin: a new orally active rifamycin. Chemotherapy 1966;11: 285–92.
  • Zhang Y, Mitchison D. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis 2003;7: 6–21.
  • Mitchison DA. The action of antituberculosis drugs in short-course chemotherapy. Tubercle 1985;66:219–25.
  • Centers for Disease Control (CDC). Transmission of multidrug-resistant TB among immuno-compromised persons in a correctional system – New York, 1991. MMWR Morb Mortal Wkly Rep 1992;41:507–9.
  • Moro ML, Gori A, Errante I, Infuso A, Franzetti F, Sodano L, et al. An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy. Italian Multidrug-Resistant Tuberculosis Outbreak Study Group. AIDS 1998;12:1095–102.
  • World Health Organization. TB – a global emergency. WHO; 1994.
  • Los Angeles Times. WHO calls tuberculosis a global emergency, April 24, 1993 [cited 2015 Feb 14]. Available from: http://articles.latimes.com/1993-04-24/news/mn-26683_1_global-emergency
  • Pablos-Mendez A, Raviglione MC, Laszlo A, Binkin N, Rieder HL, Bustreo F, et al. Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. N Engl J Med 1998;338:1641–9.
  • European Centre for Disease Prevention and Control. European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2014. Stockholm; 2014.
  • Centers for Disease Control and Prevention (CDC). Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs – worldwide, 2000-2004. MMWR Morb Mortal Wkly Rep 2006;55:301–5.
  • Liu CH, Li L, Chen Z, Wang Q, Hu YL, Zhu B, et al. Characteristics and treatment outcomes of patients with MDR and XDR tuberculosis in a TB referral hospital in Beijing: a 13-year experience. PLoS One 2011;6:e19399.
  • Almeida Da Silva PE, Palomino JC. Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs. J Antimicrob Chemother 2011;66:1417–30.
  • World Health Organization. WHO Stop TB Department, Drug-resistant tuberculosis, frequently asked questions 2012 [cited 2015 Feb 11]. Available from: http://www.who.int/tb/challenges/mdr/TDRFAQs160112final.pdf
  • Skrahina A, Hurevich H, Zalutskaya A, Sahalchyk E, Astrauko A, van Gemert W, et al. Alarming levels of drug-resistant tuberculosis in Belarus: results of a survey in Minsk. Eur Respir J 2012;39:1425–31.
  • Skrahina A, Hurevich H, Zalutskaya A, Sahalchyk E, Astrauko A, Hoffner S, et al. Multidrug-resistant tuberculosis in Belarus: the size of the problem and associated risk factors. Bull World Health Organ 2013;91:36–45.
  • Wiuff C, Zappala RM, Regoes RR, Garner KN, Baquero F, Levin BR. Phenotypic tolerance: antibiotic enrichment of noninherited resistance in bacterial populations. Antimicrob Agents Chemother 2005;49:1483–94.
  • Wakamoto Y, Dhar N, Chait R, Schneider K, Signorino-Gelo F, Leibler S, et al. Dynamic persistence of antibiotic-stressed mycobacteria. Science 2013;339:91–5.
  • Bigger JW. Treatment of staphylococcal infections with penicillin. Lancet 1944;244:497–500.
  • Zhang Y, Yew WW, Barer MR. Targeting persisters for tuberculosis control. Antimicrob Agents Chemother 2012; 56:2223–30.
  • Barlow M. What antimicrobial resistance has taught us about horizontal gene transfer. In: Gogarten M, Gogarten J, Olendzenski L, editors. Horizontal gene transfer. Methods in molecular biology, 532. Humana Press; 2009 pp 397–411.
  • Zhang Y, Heym B, Allen B, Young D, Cole S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 1992;358:591–3.
  • Tiruviluamala P, Reichman LB. Tuberculosis. Annu Rev Public Health 2002;23:403–26.
  • Zaunbrecher MA, Sikes RD Jr, Metchock B, Shinnick TM, Posey JE. Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 2009;106:20004–9.
  • Vilcheze C, Jacobs WR Jr. The mechanism of isoniazid killing: clarity through the scope of genetics. Annu Rev Microbiol 2007;61:35–50.
  • da Silva PE, Von Groll A, Martin A, Palomino JC. Efflux as a mechanism for drug resistance in Mycobacterium tuberculosis. FEMS Immunol Med Microbiol 2011; 63:1–9.
  • Zhang Y, Yew WW. Mechanisms of drug resistance in Mycobacterium tuberculosis. Int J Tuberc Lung Dis 2009; 13:1320–30.
  • Telenti A, Imboden P, Marchesi F, Schmidheini T, Bodmer T. Direct, automated detection of rifampin-resistant Mycobacterium tuberculosis by polymerase chain reaction and single-strand conformation polymorphism analysis. Antimicrob Agents Chemother 1993;37:2054–8.
  • David HL. Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl Microbiol 1970;20:810–14.
  • Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med 1993;329:784–91.
  • Koser CU, Javid B, Liddell K, Ellington MJ, Feuerriegel S, Niemann S, et al. Drug-resistance mechanisms and tuberculosis drugs. Lancet 2015;385:305–7.
  • Rozwarski DA, Grant GA, Barton DH, Jacobs WR Jr, Sacchettini JC. Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science 1998;279:98–102.
  • 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;263:227–30.
  • Quemard A, Sacchettini JC, Dessen A, Vilcheze C, Bittman R, Jacobs WR Jr, et al. Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis. Biochemistry 1995;34:8235–41.
  • Marrakchi H, Laneelle G, Quemard A. InhA, a target of the antituberculous drug isoniazid, is involved in a mycobacterial fatty acid elongation system, FAS-II. Microbiology 2000;146:289–96.
  • Middlebrook G. Sterilization of tubercle bacilli by isonicotinic acid hydrazide and the incidence of variants resistant to the drug in vitro. Am Rev Tuberc 1952;65:765–7.
  • Middlebrook G. Isoniazid-resistance and catalase activity of tubercle bacilli; a preliminary report. Am Rev Tuberc 1954;69:471–2.
  • Zhang Y, Garbe T, Young D. Transformation with katG restores isoniazid-sensitivity in Mycobacterium tuberculosis isolates resistant to a range of drug concentrations. Mol Microbiol 1993;8:521–4.
  • Sandgren A, Strong M, Muthukrishnan P, Weiner BK, Church GM, Murray MB. Tuberculosis drug resistance mutation database. PLoS Med 2009;6:e2.
  • Wengenack NL, Uhl JR, St Amand AL, Tomlinson AJ, Benson LM, Naylor S, et al. Recombinant Mycobacterium tuberculosis KatG(S315T) is a competent catalase-peroxidase with reduced activity toward isoniazid. J Infect Dis 1997;176:722–7.
  • 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;182:1788–90.
  • Morlock GP, Metchock B, Sikes D, Crawford JT, Cooksey RC. ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother 2003;47:3799–805.
  • Larsen MH, Vilcheze C, Kremer L, Besra GS, Parsons L, Salfinger M, et al. Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis. Mol Microbiol 2002;46:453–66.
  • Campbell PJ, Morlock GP, Sikes RD, Dalton TL, Metchock B, Starks AM, et al. Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2011;55:2032–41.
  • 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;43:2087–9.
  • Flores-Trevino S, Morfin-Otero R, Rodriguez-Noriega E, Hernandez Y, Rodriguez N, Gonzalez-Diaz E, et al. Phenotypic resistance profiles and gene mutations associated to isoniazid and rifampicin resistance of clinical isolates of Mycobacterium tuberculosis from Guadalajara, México. ICAAC; 2012.
  • Sherman DR, Mdluli K, Hickey MJ, Arain TM, Morris SL, Barry CE 3rd, et al. Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis. Science 1996;272:1641–3.
  • Heym B, Stavropoulos E, Honore 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;65:1395–401.
  • Kelley CL, Rouse DA, Morris SL. Analysis of ahpC gene mutations in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 1997;41:2057–8.
  • McClure WR, Cech CL. On the mechanism of rifampicin inhibition of RNA synthesis. J Biol Chem 1978;253: 8949–56.
  • 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;104:901–12.
  • Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston MJ, et al. Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet 1993; 341:647–50.
  • Miller LP, Crawford JT, Shinnick TM. The rpoB gene of Mycobacterium tuberculosis. Antimicrob Agents Chemother 1994;38:805–11.
  • Williams DL, Spring L, Collins L, Miller LP, Heifets LB, Gangadharam PR, et al. Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998;42: 1853–7.
  • Ramaswamy S, Musser JM. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber Lung Dis 1998;79:3–29.
  • Heep M, Brandstatter B, Rieger U, Lehn N, Richter E, Rusch-Gerdes S, et al. Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. J Clin Microbiol 2001;39:107–10.
  • Musser JM. Antimicrobial agent resistance in mycobacteria: molecular genetic insights. Clin Microbiol Rev 1995;8: 496–514.
  • Huitric E, Werngren J, Jureen P, Hoffner S. Resistance levels and rpoB gene mutations among in vitro-selected rifampin-resistant Mycobacterium tuberculosis mutants. Antimicrob Agents Chemother 2006;50:2860–2.
  • Van Deun A, Barrera L, Bastian I, Fattorini L, Hoffmann H, Kam KM, et al. Mycobacterium tuberculosis strains with highly discordant rifampin susceptibility test results. J Clin Microbiol 2009;47:3501–6.
  • Billington OJ, McHugh TD, Gillespie SH. Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis. Antimicrob Agents Chemother 1999;43: 1866–9.
  • Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJ. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science 2006;312:1944–6.
  • Jamieson FB, Guthrie JL, Neemuchwala A, Lastovetska O, Melano RG, Mehaffy C. Profiling of rpoB mutations and MICs for rifampin and rifabutin in Mycobacterium tuberculosis. J Clin Microbiol 2014;52:2157–62.
  • Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet 2012;44:106–10.
  • Siu GK, Zhang Y, Lau TC, Lau RW, Ho PL, Yew WW, et al. Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis. J Antimicrob Chemother 2011;66: 730–3.
  • Hatfull GF, Jacobs WR Jr, editor. Molecular genetics of mycobacteria. ASM Press; 2014.
  • Takayama K, Kilburn JO. Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. Antimicrob Agents Chemother 1989;33:1493–9.
  • Mikusova K, Slayden RA, Besra GS, Brennan PJ. Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. Antimicrob Agents Chemother 1995;39:2484–9.
  • Belanger AE, Besra GS, Ford ME, Mikusova K, Belisle JT, Brennan PJ, et al. The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc Natl Acad Sci U S A 1996; 93:11919–24.
  • Telenti A, Philipp WJ, Sreevatsan S, Bernasconi C, Stockbauer KE, Wieles B, et al. The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med 1997;3:567–70.
  • Böttger EC. The ins and outs of Mycobacterium tuberculosis drug susceptibility testing. Clin Microbiol Infect 2011;17:1128–34.
  • Griffith ME, Bodily HL. Stability of antimycobacterial drugs in susceptibility testing. Antimicrob Agents Chemother 1992;36:2398–402.
  • Madison B, Robinson-Dunn B, George I, Gross W, Lipman H, Metchock B, et al. Multicenter evaluation of ethambutol susceptibility testing of mycobacterium tuberculosis by agar proportion and radiometric methods. J Clin Microbiol 2002;40:3976–9.
  • Sreevatsan S, Stockbauer KE, Pan X, Kreiswirth BN, Moghazeh SL, Jacobs WR Jr, et al. Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations. Antimicrob Agents Chemother 1997;41:1677–81.
  • Plinke C, Cox HS, Kalon S, Doshetov D, Rusch-Gerdes S, Niemann S. Tuberculosis ethambutol resistance: concordance between phenotypic and genotypic test results. Tuberculosis 2009;89:448–52.
  • Plinke C, Rusch-Gerdes S, Niemann S. Significance of mutations in embB codon 306 for prediction of ethambutol resistance in clinical Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother 2006;50:1900–2.
  • Plinke C, Walter K, Aly S, Ehlers S, Niemann S. Mycobacterium tuberculosis embB codon 306 mutations confer moderately increased resistance to ethambutol in vitro and in vivo. Antimicrob Agents Chemother 2011;55:2891–6.
  • Safi H, Sayers B, Hazbon MH, Alland D. Transfer of embB codon 306 mutations into clinical Mycobacterium tuberculosis strains alters susceptibility to ethambutol, isoniazid, and rifampin. Antimicrob Agents Chemother 2008;52: 2027–34.
  • Starks AM, Gumusboga A, Plikaytis BB, Shinnick TM, Posey JE. Mutations at embB codon 306 are an important molecular indicator of ethambutol resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2009; 53:1061–6.
  • Ramaswamy SV, Amin AG, Goksel S, Stager CE, Dou SJ, El Sahly H, et al. Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2000;44:326–36.
  • Cui Z, Li Y, Cheng S, Yang H, Lu J, Hu Z, et al. Mutations in the embC-embA intergenic region contribute to Mycobacterium tuberculosis resistance to ethambutol. Antimicrob Agents Chemother 2014;58:6837–43.
  • Heifets L, Lindholm-Levy P. Pyrazinamide sterilizing activity in vitro against semidormant Mycobacterium tuberculosis bacterial populations. Am Rev Respir Dis 1992;145:1223–5.
  • Zhang Y, Wade MM, Scorpio A, Zhang H, Sun Z. Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid. J Antimicrob Chemother 2003;52:790–5.
  • Wade MM, Zhang Y. Anaerobic incubation conditions enhance pyrazinamide activity against Mycobacterium tuberculosis. J Med Microbiol 2004;53:769–73.
  • Scorpio A, Zhang Y. Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat Med 1996;2:662–7.
  • Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, et al. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science 2011;333:1630–2.
  • Shi W, Chen J, Feng J, Cui P, Zhang S, Weng X, et al. Aspartate decarboxylase (PanD) as a new target of pyrazinamide in Mycobacterium tuberculosis. Emerg Microbes Infect 2014;3:e58
  • Scorpio A, Lindholm-Levy P, Heifets L, Gilman R, Siddiqi S, Cynamon M, et al. Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 1997;41:540–3.
  • Miotto P, Cabibbe AM, Feuerriegel S, Casali N, Drobniewski F, Rodionova Y, et al. Mycobacterium tuberculosis pyrazinamide resistance determinants: a multicenter study. MBio 2014;5:e01819–14.
  • Hoffner S, Angeby K, Sturegard E, Jonsson B, Johansson A, Sellin M, et al. Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience. Int J Tuberc Lung Dis 2013;17: 1486–90.
  • Xia Q, Zhao LL, Li F, Fan YM, Chen YY, Wu BB, et al. Phenotypic and genotypic characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Zhejiang, China. Antimicrob Agents Chemother 2015;59:1690–5.
  • Akhmetova A, Kozhamkulov U, Bismilda V, Chingissova L, Abildaev T, Dymova M, et al. Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan. Int J Tuberc Lung Dis 2015;19:179–84.
  • Tan Y, Hu Z, Zhang T, Cai X, Kuang H, Liu Y, et al. Role of pncA and rpsA gene sequencing in detection of pyrazinamide resistance in Mycobacterium tuberculosis isolates from southern China. J Clin Microbiol 2014; 52:291–7.
  • Magnet S, Blanchard JS. Molecular insights into aminoglycoside action and resistance. Chem Rev 2005;105: 477–98.
  • Pestka S. The use of inhibitors in studies on protein synthesis. Methods Enzymol 1974;30:261–82.
  • Engström A, Perskvist N, Werngren J, Hoffner SE, Jureen P. Comparison of clinical isolates and in vitro selected mutants reveals that tlyA is not a sensitive genetic marker for capreomycin resistance in Mycobacterium tuberculosis. J Antimicrob Chemother 2011;66:1247–54.
  • Maus CE, Plikaytis BB, Shinnick TM. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2005;49:3192–7.
  • Reeves AZ, Campbell PJ, Sultana R, Malik S, Murray M, Plikaytis BB, et al. Aminoglycoside cross-resistance in Mycobacterium tuberculosis due to mutations in the 5’ untranslated region of whiB7. Antimicrob Agents Chemother 2013;57:1857–65.
  • Du Q, Dai G, Long Q, Yu X, Dong L, Huang H, et al. Mycobacterium tuberculosis rrs A1401G mutation correlates with high-level resistance to kanamycin, amikacin, and capreomycin in clinical isolates from mainland China. Diagn Microbiol Infect Dis 2013;77:138–42.
  • Chakravorty S, Lee JS, Cho EJ, Roh SS, Smith LE, Lee J, et al. Genotypic susceptibility testing of Mycobacterium tuberculosis isolates for amikacin and kanamycin resistance by use of a rapid sloppy molecular beacon-based assay identifies more cases of low-level drug resistance than phenotypic Lowenstein-Jensen testing. J Clin Microbiol 2015;53: 43–51.
  • 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;42:1295–7.
  • Georghiou SB, Magana M, Garfein RS, Catanzaro DG, Catanzaro A, Rodwell TC. Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review. PLoS One 2012;7:e33275.
  • Reeves AZ, Campbell PJ, Willby MJ, Posey JE. Disparities in capreomycin resistance levels associated with the rrs A1401G mutation in clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2015;59: 444–9.
  • Stanley RE, Blaha G, Grodzicki RL, Strickler MD, Steitz TA. The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome. Nat Struct Mol Biol 2010;17:289–93.
  • 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;23:173–82.
  • Maus CE, Plikaytis BB, Shinnick TM. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2005;49:571–7.
  • Houghton JL, Green KD, Pricer RE, Mayhoub AS, Garneau-Tsodikova S. Unexpected N-acetylation of capreomycin by mycobacterial Eis enzymes. J Antimicrob Chemother 2013;68:800–5.
  • Vos SM, Tretter EM, Schmidt BH, Berger JM. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat Rev Mol Cell Biol 2011;12:827–41.
  • Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 1997;61:377–92.
  • Schmutz E, Hennig S, Li SM, Heide L. Identification of a topoisomerase IV in actinobacteria: purification and characterization of ParYR and GyrBR from the coumermycin A1 producer Streptomyces rishiriensis DSM 40489. Microbiology 2004;150:641–7.
  • Piton J, Petrella S, Delarue M, Andre-Leroux G, Jarlier V, Aubry A, et al. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase. PLoS One 2010;5:e12245.
  • Wang JC. DNA topoisomerases. Annu Rev Biochem 1985;54:665–97.
  • Xu C, Kreiswirth BN, Sreevatsan S, Musser JM, Drlica K. Fluoroquinolone resistance associated with specific gyrase mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis. J Infect Dis 1996;174:1127–30.
  • Takiff HE, Salazar L, Guerrero C, Philipp W, Huang WM, Kreiswirth B, et al. Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob Agents Chemother 1994;38:773–80.
  • Sun Z, Zhang J, Zhang X, Wang S, Zhang Y, Li C. Comparison of gyrA gene mutations between laboratory-selected ofloxacin-resistant Mycobacterium tuberculosis strains and clinical isolates. Int J Antimicrob Agents 2008; 31:115–21.
  • Avalos E, Catanzaro D, Catanzaro A, Ganiats T, Brodine S, Alcaraz J, et al. Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review. PLoS One 2015;10:e0120470.
  • Chakravorty S, Aladegbami B, Thoms K, Lee JS, Lee EG, Rajan V, et al. Rapid detection of fluoroquinolone-resistant and heteroresistant Mycobacterium tuberculosis by use of sloppy molecular beacons and dual melting-temperature codes in a real-time PCR assay. J Clin Microbiol 2011;49: 932–40.
  • 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:e39754.
  • De Rossi E, Arrigo P, Bellinzoni M, Silva PA, Martin C, Ainsa JA, et al. The multidrug transporters belonging to major facilitator superfamily in Mycobacterium tuberculosis. Mol Med 2002;8:714–24.
  • Takiff HE, Cimino M, Musso MC, Weisbrod T, Martinez R, Delgado MB, et al. Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis. Proc Natl Acad Sci U S A 1996;93:362–6.
  • Sreevatsan S, Pan X, Stockbauer KE, Connell ND, Kreiswirth BN, Whittam TS, et al. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination. Proc Natl Acad Sci U S A 1997;94:9869–74.
  • Aubry A, Veziris N, Cambau E, Truffot-Pernot C, Jarlier V, Fisher LM. Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis: functional analysis of mutant enzymes. Antimicrob Agents Chemother 2006;50:104–12.
  • Angeby KA, Jureen P, Giske CG, Chryssanthou E, Sturegard E, Nordvall M, et al. Wild-type MIC distributions of four fluoroquinolones active against Mycobacterium tuberculosis in relation to current critical concentrations and available pharmacokinetic and pharmacodynamic data. J Antimicrob Chemother 2010;65:946–52.
  • Li J, Gao X, Luo T, Wu J, Sun G, Liu Q, et al. Association of gyrA/B mutations and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis. Emerg Microbes Infect 2014;3:e19.
  • Canetti G, Froman S, Grosset J, Hauduroy P, Langerova M, Mahler HT, et al. Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull World Health Organ 1963;29:565–78.
  • Canetti G, Fox W, Khomenko A, Mahler HT, Menon NK, Mitchison DA, et al. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes. Bull World Health Organ 1969;41:21–43.
  • World Health Organization. Molecular line probe assays for rapid screening of patients at risk of multidrug-resistant tuberculosis (MDR-TB) 2008 [cited 2015 Mar 30]. Available from: http://www.who.int/tb/features_archive/policy_statement.pdf
  • Folkvardsen DB, Svensson E, Thomsen VO, Rasmussen EM, Bang D, Werngren J, et al. Can molecular methods detect 1% isoniazid resistance in Mycobacterium tuberculosis? J Clin Microbiol 2013;51:1596–9.
  • Chakravorty S, Kothari H, Aladegbami B, Cho EJ, Lee JS, Roh SS, et al. Rapid, high-throughput detection of rifampin resistance and heteroresistance in Mycobacterium tuberculosis by use of sloppy molecular beacon melting temperature coding. J Clin Microbiol 2012;50:2194–202.
  • Engström A, Hoffner S, Jureen P. Detection of heteroresistant Mycobacterium tuberculosis by pyrosequencing. J Clin Microbiol 2013;51:4210–12.
  • Nebenzahl-Guimaraes H, Jacobson KR, Farhat MR, Murray MB. Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis. J Antimicrob Chemother 2014;69:331–42.
  • Andries K, Verhasselt P, Guillemont J, Gohlmann HW, Neefs JM, Winkler H, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005;307:223–7.
  • Matsumoto M, Hashizume H, Tomishige T, Kawasaki M, Tsubouchi H, Sasaki H, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med 2006;3:e466.
  • Sanchez-Padilla E, Merker M, Beckert P, Jochims F, Dlamini T, Kahn P, et al. Detection of drug-resistant tuberculosis by Xpert MTB/RIF in Swaziland. N Engl J Med 2015;372:1181–2.
  • Varela G, Gonzalez S, Gadea P, Coitinho C, Mota I, Gonzalez G, et al. Prevalence and dissemination of the Ser315Thr substitution within the KatG enzyme in isoniazid-resistant strains of Mycobacterium tuberculosis isolated in Uruguay. J Med Microbiol 2008;57:1518–22.
  • Bergval I, Sengstake S, Brankova N, Levterova V, Abadia E, Tadumaze N, et al. Combined species identification, genotyping, and drug resistance detection of Mycobacterium tuberculosis cultures by MLPA on a bead-based array. PLoS One 2012;7:e43240.
  • Bergval IL, Vijzelaar RN, Dalla Costa ER, Schuitema AR, Oskam L, Kritski AL, et al. Development of multiplex assay for rapid characterization of Mycobacterium tuberculosis. J Clin Microbiol 2008;46:689–99.
  • Engström A, Zardán Gómez de la Torre T, Strømme M, Nilsson M, Herthnek D. Detection of rifampicin resistance in Mycobacterium tuberculosis by padlock probes and magnetic nanobead-based readout. PLoS One 2013;8: e62015.
  • Lee MF, Chen YH, Hsu HJ, Peng CF. One-tube loop-mediated isothermal amplification combined with restriction endonuclease digestion and ELISA for colorimetric detection of resistance to isoniazid, ethambutol and streptomycin in Mycobacterium tuberculosis isolates. J Microbiol Methods 2010;83:53–8.
  • Rice JE, Reis AH Jr, Rice LM, Carver-Brown RK, Wangh LJ. Fluorescent signatures for variable DNA sequences. Nucleic Acids Res 2012;40:e164.
  • Cheng AF, Yew WW, Chan EW, Chin ML, Hui MM, Chan RC. Multiplex PCR amplimer conformation analysis for rapid detection of gyrA mutations in fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates. Antimicrob Agents Chemother 2004;48:596–601.
  • Hernandez-Neuta I, Varela A, Martin A, von Groll A, Jureen P, Lopez B, et al. Rifampin-isoniazid oligonucleotide typing: an alternative format for rapid detection of multidrug-resistant Mycobacterium tuberculosis. J Clin Microbiol 2010;48:4386–91.
  • Gomgnimbou MK, Abadia E, Zhang J, Refregier G, Panaiotov S, Bachiyska E, et al. “Spoligoriftyping,” a dual-priming-oligonucleotide-based direct-hybridization assay for tuberculosis control with a multianalyte microbead-based hybridization system. J Clin Microbiol 2012;50: 3172–9.
  • Veigas B, Machado D, Perdigao J, Portugal I, Couto I, Viveiros M, et al. Au-nanoprobes for detection of SNPs associated with antibiotic resistance in Mycobacterium tuberculosis. Nanotechnology 2010;21:415101.
  • Cornett EM, Campbell EA, Gulenay G, Peterson E, Bhaskar N, Kolpashchikov DM. Molecular logic gates for DNA analysis: detection of rifampin resistance in M. tuberculosis DNA. Angew Chem Int Ed Engl 2012;51: 9075–7.
  • Liang C, Chu Y, Cheng S, Wu H, Kajiyama T, Kambara H, et al. Multiplex loop-mediated isothermal amplification detection by sequence-based barcodes coupled with nicking endonuclease-mediated pyrosequencing. Anal Chem 2012; 84:3758–63.
  • Markoulatos P, Siafakas N, Moncany M. Multiplex polymerase chain reaction: a practical approach. J Clin Lab Anal 2002;16:47–51.
  • Akhras MS, Thiyagarajan S, Villablanca AC, Davis RW, Nyren P, Pourmand N. PathogenMip assay: a multiplex pathogen detection assay. PLoS One 2007;2:e223.
  • Folkvardsen DB, Thomsen VO, Rigouts L, Rasmussen EM, Bang D, Bernaerts G, et al. Rifampin heteroresistance in Mycobacterium tuberculosis cultures as detected by phenotypic and genotypic drug susceptibility test methods. J Clin Microbiol 2013;51:4220–2.
  • Pholwat S, Stroup S, Foongladda S, Houpt E. Digital PCR to detect and quantify heteroresistance in drug resistant Mycobacterium tuberculosis. PLoS One 2013;8:e57238.
  • Meldrum C, Doyle MA, Tothill RW. Next-generation sequencing for cancer diagnostics: a practical perspective. Clin Biochem Rev 2011;32:177–95.
  • Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E, et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet 2015;47:242–9.
  • Hillemann D, Rusch-Gerdes S, Richter E. Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin-capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol 2009;47:1767–72.
  • Hillemann D, Rusch-Gerdes S, Richter E. Evaluation of the GenoType MTBDRplus assay for rifampin and isoniazid susceptibility testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol 2007;45: 2635–40.
  • Jureen P, Werngren J, Hoffner SE. Evaluation of the line probe assay (LiPA) for rapid detection of rifampicin resistance in Mycobacterium tuberculosis. Tuberculosis 2004;84: 311–16.
  • Mitarai S, Kato S, Ogata H, Aono A, Chikamatsu K, Mizuno K, et al. Comprehensive multicenter evaluation of a new line probe assay kit for identification of Mycobacterium species and detection of drug-resistant Mycobacterium tuberculosis. J Clin Microbiol 2012;50:884–90.
  • Espasa M, Gonzalez-Martin J, Alcaide F, Aragon LM, Lonca J, Manterola JM, et al. Direct detection in clinical samples of multiple gene mutations causing resistance of Mycobacterium tuberculosis to isoniazid and rifampicin using fluorogenic probes. J Antimicrob Chemother 2005; 55:860–5.
  • van Doorn HR, An DD, de Jong MD, Lan NT, Hoa DV, Quy HT, et al. Fluoroquinolone resistance detection in Mycobacterium tuberculosis with locked nucleic acid probe real-time PCR. Int J Tuberc Lung Dis 2008;12:736–42.
  • Piatek AS, Tyagi S, Pol AC, Telenti A, Miller LP, Kramer FR, et al. Molecular beacon sequence analysis for detecting drug resistance in Mycobacterium tuberculosis. Nat Biotechnol 1998;16:359–63.
  • Higuchi R, Dollinger G, Walsh PS, Griffith R. Simultaneous amplification and detection of specific DNA sequences. Biotechnology 1992;10:413–17.
  • Helb D, Jones M, Story E, Boehme C, Wallace E, Ho K, et al. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol 2010;48:229–37.
  • World Health Organization. WHO endorses new rapid tuberculosis test 2010 [cited 2015 Mar 14]. Available from: http://www.who.int/mediacentre/news/releases/2010/tb_test_20101208/en/index.html
  • World Health Organization. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF System. WHO; 2011.
  • Vassall A, van Kampen S, Sohn H, Michael JS, John KR, den Boon S, et al. Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis. PLoS Med 2011;8:e1001120.
  • Kirwan DE, Cardenas MK, Gilman RH. Rapid implementation of new TB diagnostic tests: is it too soon for a global roll-out of Xpert MTB/RIF? Am J Trop Med Hyg 2012;87:197–201.
  • Morey M, Fernandez-Marmiesse A, Castineiras D, Fraga JM, Couce ML, Cocho JA. A glimpse into past, present, and future DNA sequencing. Mol Genet Metab 2013;110:3–24.
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 1977;74:5463–7.
  • Ronaghi M, Uhlén M, Nyrén P. A sequencing method based on real-time pyrophosphate. Science 1998;281:363, 365.
  • Engström A, Morcillo N, Imperiale B, Hoffner SE, Jureen P. Detection of first- and second-line drug resistance in Mycobacterium tuberculosis clinical isolates by pyrosequencing. J Clin Microbiol 2012;50:2026–33.
  • Lam HY, Clark MJ, Chen R, Chen R, Natsoulis G, O’Huallachain M, et al. Performance comparison of whole-genome sequencing platforms. Nat Biotechnol 2012; 30:78–82.
  • Daum LT, Rodriguez JD, Worthy SA, Ismail NA, Omar SV, Dreyer AW, et al. Next-generation ion torrent sequencing of drug resistance mutations in Mycobacterium tuberculosis strains. J Clin Microbiol 2012;50:3831–7.
  • Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 2005;437:376–80.
  • Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, et al. Accurate multiplex polony sequencing of an evolved bacterial genome. Science 2005;309: 1728–32.
  • Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 2010;327:78–81.
  • Grada A, Weinbrecht K. Next-generation sequencing: methodology and application. J Invest Dermatol 2013; 133:e11.
  • Kasianowicz JJ, Brandin E, Branton D, Deamer DW. Characterization of individual polynucleotide molecules using a membrane channel. Proc Natl Acad Sci U S A 1996;93:13770–3.
  • Levene MJ, Korlach J, Turner SW, Foquet M, Craighead HG, Webb WW. Zero-mode waveguides for single-molecule analysis at high concentrations. Science 2003;299:682–6.
  • Feuerriegel S, Schleusener V, Beckert P, Kohl TA, Miotto P, Cirillo DM, et al. PhyResSE: web tool delineating Mycobacterium tuberculosis antibiotic resistance and lineage from whole-genome sequencing data. J Clin Microbiol 2015;53:1908–14.
  • Steiner A, Stucki D, Coscolla M, Borrell S, Gagneux S. KvarQ: targeted and direct variant calling from fastq reads of bacterial genomes. BMC Genomics 2014;15:881.

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