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The impact of drug resistance on Mycobacterium tuberculosis physiology: what can we learn from rifampicin?

Anastasia KochMedical Research Council/National Health Laboratory Service/University of Cape Town Molecular Mycobacteriology Research Unit, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town 7701, South Africa
,
Valerie Mizrahi
&
Digby F WarnerCorrespondence[email protected]
Pages 1-11 | Received 23 Sep 2015, Accepted 02 Nov 2015, Published online: 25 Jan 2019

  • Cars O, Hogberg LD, Murray M et al.Meeting the challenge of antibiotic resistance. BMJ2008;337: a1438.
  • Martinez JL, Fajardo A, Garmendia L et al.A global view of antibiotic resistance. FEMS Microbiol Rev2009;33: 44–65.
  • World Health Organization. Global tuberculosis report 2013. Geneva: WHO, 2013.Available at http://www.who.int/tb/publications/global_report/en/index.html (accessed 12 December 2013).
  • Pooran A, Pieterson E, Davids M, Theron G, Dheda K.What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa? PLoS ONE2013;8: e54587.
  • Fischbach MA, Walsh CT.Antibiotics for emerging pathogens. Science2009;325: 1089–1093.
  • Gandhi NR, Nunn P, Dheda K et al.Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet2010;375: 1830–1843.
  • Colijn C, Cohen T, Ganesh A, Murray M.Spontaneous emergence of multiple drug resistance in tuberculosis before and during therapy. PLoS ONE2011;6: e18327.
  • Blower SM, Chou T.Modeling the emergence of the ‘hot zones’: tuberculosis and the amplification dynamics of drug resistance. Nat Med2004;10: 1111–1116.
  • Muller B, Borrell S, Rose G, Gagneux S.The heterogeneous evolution of multidrug-resistant Mycobacterium tuberculosis. Trends Genet2012;29: 160–169.
  • Farhat MR, Shapiro BJ, Kieser K et al.Genomic analysis identifies targets of convergent positive selection in drug resistant Mycobacterium tuberculosis. Nat Genet2013;45: 1183–1189.
  • Zhang H, Li D, Zhao L et al.Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat Genet2013;45: 1255–1260.
  • Sandgren A, Strong M, Muthukrishnan P, Weiner BK, Church GM, Murray MB.Tuberculosis drug resistance mutation database. PLoS Med2009;6: e2.
  • Casali N, Nikolayevskyy V, Balabanova Y et al.Microevolution of extensively drug-resistant tuberculosis in Russia. Genome Res2012;22: 735–745.
  • Ioerger TR, Feng Y, Chen X et al.The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa. BMC Genomics2010;11: 670.
  • Sun G, Luo T, Yang C et al.Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. J Infect Dis2012;206: 1724–1733.
  • Andersson DI, Hughes D.Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol2010;8: 260–271.
  • Borukhov S, Nudler E.RNA polymerase: the vehicle of transcription. Trends Microbiol2008;16: 126–134.
  • Campbell EA, Korzheva N, Mustaev A et al.Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell2001;104: 901–912.
  • Comas I, Coscolla M, Luo T et al.Out-of-Africa migration and Neolithic co-expansion of tuberculosis with modern humans. Nat Genet2013;45: 1176–1182.
  • Mitchison DA.Role of individual drugs in the chemotherapy of tuberculosis. Int J Tuberc Lung Dis2000;4: 796–806.
  • Forrest GN, Tamura K.Rifampin combination therapy for nonmycobacterial infections. Clin Microbiol Rev2010;23: 14–34.
  • Lipsitch M, Levin BR.The population dynamics of antimicrobial chemotherapy. Antimicrob Agents Chemother1997;41: 363–373.
  • Xie Z, Siddiqi N, Rubin EJ.Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother2005;49: 4778–4780.
  • Piccaro G, Giannoni F, Filippini P, Mustazzolu A, Fattorini L.Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions. Antimicrob Agents Chemother2013;57: 1428–1433.
  • Sala C, Dhar N, Hartkoorn RC et al.Simple model for testing drugs against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother2010;54: 4150–4158.
  • Connolly LE, Edelstein PH, Ramakrishnan L.Why is long-term therapy required to cure tuberculosis? PLoS Med2007;4: e120.
  • Barry CE 3rd, Boshoff HI, Dartois V et al.The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol2009;7: 845–855.
  • Rittershaus ES, Baek SH, Sassetti CM.The normalcy of dormancy: common themes in microbial quiescence. Cell Host Microbe2013;13: 643–651.
  • Donald PR, van Helden PD.The global burden of tuberculosis—combating drug resistance in difficult times. N Engl J Med2009;360: 2393–2395.
  • Zhang G, Campbell EA, Minakhin L, Richter C, Severinov K, Darst SA.Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 A resolution. Cell1999;98: 811–824.
  • Borukhov S, Nudler E.RNA polymerase holoenzyme: structure, function and biological implications. Curr Opin Microbiol2003;6: 93–100.
  • Ramaswamy S, Musser JM.Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber Lung Dis1998;79: 3–29.
  • Jin DJ, Gross CA.Mapping and sequencing of mutations in the Escherichia coli rpoB gene that lead to rifampicin resistance. J Mol Biol1988;202: 45–58.
  • Zhang Y, Telenti A. Genetics of drug resistance in Mycobacterium tuberculosis. Molecular genetics of mycobacteria. Washington, DC: ASM Press, 2000.
  • Heep M, Brandstatter B, Rieger U et al.Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. J Clin Microbiol2001;39: 107–110.
  • Heep M, Odenbreit S, Beck D et al.Mutations at four distinct regions of the rpoB gene can reduce the susceptibility of Helicobacter pylori to rifamycins. Antimicrob Agents Chemother2000;44: 1713–1715.
  • Telenti A, Imboden P, Marchesi F et al.Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet1993;341: 647–650.
  • Zhou YN, Jin DJ.The rpoB mutants destabilizing initiation complexes at stringently controlled promoters behave like “stringent” RNA polymerases in Escherichia coli. Proc Natl Acad Sci USA1998;95: 2908–2913.
  • Hosaka T, Ohnishi-Kameyama M, Muramatsu H et al.Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12. Nat Biotechnol2009;27: 462–464.
  • Singer M, Jin DJ, Walter WA, Gross CA.Genetic evidence for the interaction between cluster I and cluster III rifampicin resistant mutations. J Mol Biol1993;231: 1–5.
  • Jin DJ, Gross CA.Characterization of the pleiotropic phenotypes of rifampin-resistant rpoB mutants of Escherichia coli. J Bacteriol1989;171: 5229–5231.
  • Jin DJ, Gross CA.RpoB8, a rifampicin-resistant termination-proficient RNA polymerase, has an increased Km for purine nucleotides during transcription elongation. J Biol Chem1991;266: 14478–14485.
  • Jin DJ, Walter WA, Gross CA.Characterization of the termination phenotypes of rifampicin-resistant mutants. J Mol Biol1988;202: 245–253.
  • Landick R, Stewart J, Lee DN.Amino acid changes in conserved regions of the beta-subunit of Escherichia coli RNA polymerase alter transcription pausing and termination. Genes Dev1990;4: 1623–1636.
  • Yanofsky C, Horn V.Rifampin resistance mutations that alter the efficiency of transcription termination at the tryptophan operon attenuator. J Bacteriol1981;145: 1334–1341.
  • Ingham CJ, Furneaux PA.Mutations in the ss subunit of the Bacillus subtilis RNA polymerase that confer both rifampicin resistance and hypersensitivity to NusG. Microbiology2000;146: 3041–3049.
  • Trautinger BW, Lloyd RG.Modulation of DNA repair by mutations flanking the DNA channel through RNA polymerase. EMBO J2002;21: 6944–6953.
  • Ganesan AK, Smith AJ, Savery NJ, Zamos P, Hanawalt PC.Transcription coupled nucleotide excision repair in Escherichia coli can be affected by changing the arginine at position 529 of the beta subunit of RNA polymerase. DNA Repair (Amst)2007;6: 1434–1440.
  • Baharoglu Z, Lestini R, Duigou S, Michel B.RNA polymerase mutations that facilitate replication progression in the rep uvrD recF mutant lacking two accessory replicative helicases. Mol Microbiol2010;77: 324–336.
  • Dabbs ER.New tool for studying interactions of components of ribonucleic acid polymerase: rifampin-dependent mutants. J Bacteriol1979;139: 1072–1074.
  • Zhong M, Wang Y, Sun C, Yin H, Wang A, Lou L.[Growth of rifampin-dependent Mycobacterium tuberculosis in conditions without rifampin]. Zhonghua Jie He He Hu Xi Za Zhi2002;25: 588–590.Chinese.
  • Zhong M, Zhang X, Wang Y et al.An interesting case of rifampicin-dependent/-enhanced multidrug-resistant tuberculosis. Int J Tuberc Lung Dis2010;14: 40–44.
  • Honore N, Marchal G, Cole ST.Novel mutation in 16S rRNA associated with streptomycin dependence in Mycobacterium tuberculosis. Antimicrob Agents Chemother1995;39: 769–770.
  • Mokrousov I.Multiple rpoB mutants of Mycobacterium tuberculosis and second-order selection. Emerg Infect Dis2004;10: 1337–1338.
  • Lindahl T.Instability and decay of the primary structure of DNA. Nature1993;362: 709–715.
  • Warner DF.The role of DNA repair in M. tuberculosis pathogenesis. Drug Discov Today2010;7: e5–e11.
  • Ehrt S, Schnappinger D.Mycobacterial survival strategies in the phagosome: defence against host stresses. Cell Microbiol2009;11: 1170–1178.
  • O'Sullivan DM, McHugh TD, Gillespie SH.Analysis of rpoB and pncA mutations in the published literature: an insight into the role of oxidative stress in Mycobacterium tuberculosis evolution? J Antimicrob Chemother2005;55: 674–679.
  • Ford CB, Shah RR, Maeda MK et al.Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat Genet2013;45: 784–790.
  • Siu GK, Zhang Y, Lau TC et al.Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis. J Antimicrob Chemother2011;66: 730–733.
  • Van Deun A, Martin A, Palomino JC.Diagnosis of drug-resistant tuberculosis: reliability and rapidity of detection. Int J Tuberc Lung Dis2010;14: 131–140.
  • Lindsey HA, Gallie J, Taylor S, Kerr B.Evolutionary rescue from extinction is contingent on a lower rate of environmental change. Nature2013;494: 463–467.
  • Jenkins C, Bacon J, Allnutt J et al.Enhanced heterogeneity of rpoB in Mycobacterium tuberculosis found at low pH. J Antimicrob Chemother2009;63: 1118–1120.
  • Mariam DH, Mengistu Y, Hoffner SE, Anderson DI.Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis. Antimicrob Agents Chemother2004;48: 1289–1294.
  • Andersson DI.The biological cost of mutational antibiotic resistance: any practical conclusions? Curr Opin Microbiol2006;9: 461–465.
  • Gagneux S, Burgos MV, DeRiemer K et al.Impact of bacterial genetics on the transmission of isoniazid-resistant Mycobacterium tuberculosis. PLos Pathog2006;2: e61.
  • Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJ.The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science2006;312: 1944–1946.
  • Cohen T, Murray M.Modeling epidemics of multidrug-resistant M. tuberculosis of heterogenous fitness. Nat Med2004;10: 1117–1121.
  • Borrell S, Gagneux S.Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis2009;13: 1456–1466.
  • Brandis G, Hughes D.Genetic characterization of compensatory evolution in strains carrying rpoB Ser531Leu, the rifampicin resistance mutation most frequently found in clinical isolates. J Antimicrob Chemother2013;68: 2493–2497.
  • Billington OJ, McHugh TD, Gillespie SH.Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis. Antimicrob Agents Chemother1999;43: 1866–1869.
  • Davies AP, Billington OJ, Bannister BA, Weir WR, McHugh TD, Gillespie SH.Comparison of fitness of two isolates of Mycobacterium tuberculosis, one of which had developed multi-drug resistance during the course of treatment. J Infect2000;41: 184–187.
  • Gillespie SH, Billington OJ, Breathnach A, McHugh TD.Multiple drug-resistant Mycobacterium tuberculosis: evidence for changing fitness following passage through human hosts. Microb Drug Resist2002;8: 273–279.
  • Kolter R, Siegele DA, Tormo A.The stationary phase of the bacterial life cycle. Annu Rev Microbiol1993;47: 855–874.
  • Wrande M, Roth JR, Hughes D.Accumulation of mutants in “aging” bacterial colonies is due to growth under selection, not stress-induced mutagenesis. Proc Natl Acad Sci USA2008;105: 11863–11868.
  • Barczak AK, Domenech P, Boshoff HI et al.In vivo phenotypic dominance in mouse mixed infections with Mycobacterium tuberculosis clinical isolates. J Infect Dis2005;192: 600–606.
  • Subbian S, Bandyopadhyay N, Tsenova L et al.Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary infection in rabbits. Cell Commun Signal2013;11: 60.
  • Safi H, Lingaraju S, Amin A et al.Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-d-arabinose biosynthetic and utilization pathway genes. Nat Genet2013;45: 1190–1197.
  • Comas I, Borrell S, Roetzer A et al.Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet2012;44: 106–110.
  • Firdessa R, Berg S, Hailu E et al.Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerg Infect Dis2013;19: 460–463.
  • de Vos M, Muller B, Borrell S et al.Putative compensatory mutations in the rpoC gene of rifampin-resistant Mycobacterium tuberculosis are associated with ongoing transmission. Antimicrob Agents Chemother2013;57: 827–832.
  • Brandis G, Wrande M, Liljas L, Hughes D.Fitness-compensatory mutations in rifampicin-resistant RNA polymerase. Mol Microbiol2012;85: 142–151.
  • Cordell HJ.Epistasis: what it means, what it doesn’t mean, and statistical methods to detect it in humans. Hum Mol Genet2002;11: 2463–2468.
  • Trindade S, Sousa A, Xavier KB, Dionisio F, Ferreira MG, Gordo I.Positive epistasis drives the acquisition of multidrug resistance. PLoS Genet2009;5: e1000578.
  • Baker S, Duy PT, Nga TV et al.Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure. Elife2013;2: e01229.
  • Hall AR, James IC, Maclean C.The fitness cost of rifampicin resistance in Pseudomonas aeruginosa depends on demand for RNA polymerase. Genetics2011;187: 817–822.
  • Bergval I, Kwok B, Schuitema A et al.Pre-existing isoniazid resistance, but not the genotype of Mycobacterium tuberculosis drives rifampicin resistance codon preference in vitro. PLoS ONE2012;7: e29108.
  • Hazbon MH, Brimacombe M, Bobadilla del Valle M et al.Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother2006;50: 2640–2649.
  • 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 Dis2000;182: 1788–1790.
  • Borrell S, Teo Y, Giardina F et al.Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis. EMPH2013;2013: 65–74.
  • Rovinskiy N, Agbleke AA, Chesnokova O, Pang Z, Higgins NP.Rates of gyrase supercoiling and transcription elongation control supercoil density in a bacterial chromosome. PLoS Genet2012;8: e1002845.
  • Gagneux S, DeRiemer K, Van T et al.Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc Natl Acad Sci USA2006;103: 2869–2873.
  • Shcherbakov D, Akbergenov R, Matt T, Sander P, Andersson DI, Bottger EC.Directed mutagenesis of Mycobacterium smegmatis 16S rRNA to reconstruct the in-vivo evolution of aminoglycoside resistance in Mycobacterium tuberculosis. Mol Microbiol2010;77: 830–840.
  • Saunders NJ, Trivedi UH, Thomson ML, Doig C, Laurenson IF, Blaxter ML.Deep resequencing of serial sputum isolates of Mycobacterium tuberculosis during therapeutic failure due to poor compliance reveals stepwise mutation of key resistance genes on an otherwise stable genetic background. J Infect2011;62: 212–217.
  • Drobniewski FA, Caws M, Gibson A, Young D.Modern laboratory diagnosis of tuberculosis. Lancet Infect Dis2003;3: 141–147.
  • Strauss O, Warren R, Jordaan A et al.Spread of a low-fitness drug-resistant Mycobacterium tuberculosis strain in a setting of high human immunodeficiency virus prevalence. J Clin Microbiol2008;46: 1514–1516.
  • Malhotra S, Cook VJ, Wolfe JN, Tang P, Elwood K, Sharma MK.A mutation in Mycobacterium tuberculosis rpoB gene confers rifampin resistance in three HIV-TB cases. Tuberculosis (Edinb)2010;90: 152–157.
  • Motiwala AS, Dai Y, Jones-Lopez EC et al.Mutations in extensively drug-resistant Mycobacterium tuberculosis that do not code for known drug-resistance mechanisms. J Infect Dis2010;201: 881–888.
  • Lane WJ, Darst SA.Molecular evolution of multisubunit RNA polymerases: sequence analysis. J Mol Biol2010;395: 671–685.
  • Lane WJ, Darst SA.Molecular evolution of multisubunit RNA polymerases: structural analysis. J Mol Biol2010;395: 686–704.
  • Nicholson WL, Maughan H.The spectrum of spontaneous rifampin resistance mutations in the rpoB gene of Bacillus subtilis 168 spores differs from that of vegetative cells and resembles that of Mycobacterium tuberculosis. J Bacteriol2002;184: 4936–4940.
  • Maughan H, Galeano B, Nicholson WL.Novel rpoB mutations conferring rifampin resistance on Bacillus subtilis: global effects on growth, competence, sporulation, and germination. J Bacteriol2004;186: 2481–2486.
  • Perkins AE, Nicholson WL.Uncovering new metabolic capabilities of Bacillus subtilis using phenotype profiling of rifampin-resistant rpoB mutants. J Bacteriol2008;190: 807–814.
  • Xu J, Tozawa Y, Lai C, Hayashi H, Ochi K.A rifampicin resistance mutation in the rpoB gene confers ppGpp-independent antibiotic production in Streptomyces coelicolor A3(2). Mol Genet Genomics2002;268: 179–189.
  • Hu H, Zhang Q, Ochi K.Activation of antibiotic biosynthesis by specified mutations in the rpoB gene (encoding the RNA polymerase beta subunit) of Streptomyces lividans. J Bacteriol2002;184: 3984–3991.
  • Inaoka T, Takahashi K, Yada H, Yoshida M, Ochi K.RNA polymerase mutation activates the production of a dormant antibiotic 3,3′-neotrehalosadiamine via an autoinduction mechanism in Bacillus subtilis. J Biol Chem2004;279: 3885–3892.
  • Murphy H, Cashel M.Isolation of RNA polymerase suppressors of a (p) ppGpp deficiency. Methods Enzymol2003;371: 596–601.
  • Applebee MK, Herrgard MJ, Palsson BO.Impact of individual mutations on increased fitness in adaptively evolved strains of Escherichia coli. J Bacteriol2008;190: 5087–5094.
  • Conrad TM, Frazier M, Joyce AR et al.RNA polymerase mutants found through adaptive evolution reprogram Escherichia coli for optimal growth in minimal media. Proc Natl Acad Sci USA2010;107: 20500–20505.
  • Herring CD, Raghunathan A, Honisch C et al.Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale. Nat Genet2006;38: 1406–1412.
  • Rodriguez-Verdugo A, Gaut BS, Tenaillon O.Evolution of Escherichia coli rifampicin resistance in an antibiotic-free environment during thermal stress. BMC Evol Biol2013;13: 50.
  • Louw GE, Warren RM, Gey van Pittius NC et al.Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux. Am J Respir Crit Care Med2011;184: 269–276.
  • Bisson GP, Mehaffy C, Broeckling C et al.Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampin-resistant, rpoB mutant Mycobacterium tuberculosis. J Bacteriol2012;194: 6441–6452.
  • du Preez I, Loots D.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. Omics2012;16: 596–603.
  • Bergval IL, Klatser PR, Schuitema AR, Oskam L, Anthony RM.Specific mutations in the Mycobacterium tuberculosis rpoB gene are associated with increased dnaE2 expression. FEMS Microbiol Lett2007;275: 338–343.
  • Abadi FJ, Carter PE, Cash P, Pennington TH.Rifampin resistance in Neisseria meningitidis due to alterations in membrane permeability. Antimicrob Agents Chemother1996;40: 646–651.
  • Tala A, Wang G, Zemanova M, Okamoto S, Ochi K, Alifano P.Activation of dormant bacterial genes by Nonomuraea sp. strain ATCC 39727 mutant-type RNA polymerase. J Bacteriol2009;191: 805–814.
  • Vigliotta G, Tredici SM, Damiano F et al.Natural merodiploidy involving duplicated rpoB alleles affects secondary metabolism in a producer actinomycete. Mol Microbiol2005;55: 396–412.
  • Ishikawa J, Chiba K, Kurita H, Satoh H.Contribution of rpoB2 RNA polymerase beta subunit gene to rifampin resistance in Nocardia species. Antimicrob Agents Chemother2006;50: 1342–1346.
  • Yu J, Wu J, Francis KP, Purchio TF, Kadurugamuwa JL.Monitoring in vivo fitness of rifampicin-resistant Staphylococcus aureus mutants in a mouse biofilm infection model. J Antimicrob Chemother2005;55: 528–534.
  • Cui L, Isii T, Fukuda M et al.An RpoB mutation confers dual heteroresistance to daptomycin and vancomycin in Staphylococcus aureus. Antimicrob Agents Chemother2010;54: 5222–5233.
  • Watanabe Y, Cui L, Katayama Y, Kozue K, Hiramatsu K.Impact of rpoB mutations on reduced vancomycin susceptibility in Staphylococcus aureus. J Clin Microbiol2011;49: 2680–2684.
  • Ochi K.Metabolic initiation of differentiation and secondary metabolism by Streptomyces griseus: significance of the stringent response (ppGpp) and GTP content in relation to A factor. J Bacteriol1987;169: 3608–3616.
  • Artsimovitch I, Patlan V, Sekine S et al.Structural basis for transcription regulation by alarmone ppGpp. Cell2004;117: 299–310.
  • Koskiniemi S, Pranting M, Gullberg E, Nasvall J, Andersson DI.Activation of cryptic aminoglycoside resistance in Salmonella enterica. Mol Microbiol2011;80: 1464–1478.
  • Primm TP, Andersen SJ, Mizrahi V, Avarbock D, Rubin H, Barry CE 3rd.The stringent response of Mycobacterium tuberculosis is required for long-term survival. J Bacteriol2000;182: 4889–4898.
  • Dahl JL, Kraus CN, Boshoff HI et al.The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc Natl Acad Sci USA2003;100: 10026–10031.
  • Jackson M, Stadthagen G, Gicquel B.Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium tuberculosis: biosynthesis, transport, regulation and biological activities. Tuberculosis (Edinb)2007;87: 78–86.
  • Matsuo M, Hishinuma T, Katayama Y, Cui L, Kapi M, Hiramatsu K.Mutation of RNA polymerase β subunit (rpoB) promotes hVISA-to-VISA phenotypic conversion of strain Mu3. Antimicrob Agents Chemother2011;55: 4188–4195.
  • Ehrt S, Rhee K.Mycobacterium tuberculosis metabolism and host interaction: mysteries and paradoxes. Curr Top Microbiol Immunol2013;374: 163–188.
  • Russell DG.Mycobacterium tuberculosis and the intimate discourse of a chronic infection. Immunol Rev2011;240: 252–268.
  • Ernst JD.The immunological life cycle of tuberculosis. Nat Rev Immunol2012;12: 581–591.
  • Lee J, Song C, Kim C et al.Profiles of IFN-γ and its regulatory cytokines (IL-12, IL-18 and IL-10) in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis. Clin Exp Immunol2002;128: 516–524.
  • Prasad TS, Verma R, Kumar S et al.Proteomic analysis of purified protein derivative of Mycobacterium tuberculosis. Clin Proteomics2013;10: 8.
  • van Pinxteren LA, Ravn P, Agger EM, Pollock J, Andersen P.Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clin Diagn Lab Immunol2000;7: 155–160.
  • Fortes A, Pereira K, Antas PR et al.Detection of in vitro interferon-gamma and serum tumour necrosis factor-alpha in multidrug-resistant tuberculosis patients. Clin Exp Immunol2005;141: 541–548.
  • de Araujo-Filho JA, Vasconcelos AC Jr, Martins de Sousa E, Kipnis A, Ribeiro E, Junqueira-Kipnis AP.Cellular responses to MPT-51, GlcB and ESAT-6 among MDR-TB and active tuberculosis patients in Brazil. Tuberculosis (Edinb)2008;88: 474–481.
  • Castro AZ, Diaz-Bardalez BM, Oliveira EC et al.Abnormal production of transforming growth factor β and interferon γ by peripheral blood cells of patients with multidrug-resistant pulmonary tuberculosis in Brazil. J Infect2005;51: 318–324.
  • Wu YE, Peng WG, Cai YM et al.Decrease in CD4+ CD25+ FoxP3+ Treg cells after pulmonary resection in the treatment of cavity multidrug-resistant tuberculosis. Int J Infect Dis2010;14: e815.
  • Karunakaran P, Davies J.Genetic antagonism and hypermutability in Mycobacterium smegmatis. J Bacteriol2000;182: 3331–3335.
  • Bjedov I, Tenaillon O, Gerard B et al.Stress-induced mutagenesis in bacteria. Science2003;300: 1404–1409.
  • Cairns J, Overbaugh J, Miller S.The origin of mutants. Nature1988;335: 142–145.
  • Rosenberg SM, Hastings PJ.Adaptive point mutation and adaptive amplification pathways in the Escherichia coli Lac system: stress responses producing genetic change. J Bacteriol2004;186: 4838–4843.
  • Katz S, Hershberg R.Elevated mutagenesis does not explain the increased frequency of antibiotic resistant mutants in starved aging colonies. PLOS Genet2013;9: e1003968.
  • Dragosits M, Mozhayskiy V, Quinones-Soto S, Park J, Tagkopoulos I.Evolutionary potential, cross-stress behavior and the genetic basis of acquired stress resistance in Escherichia coli. Mol Syst Biol2013;9: 643.
  • Webber MA, Ricci V, Whitehead R et al.Clinically relevant mutant DNA gyrase alters supercoiling, changes the transcriptome, and confers multidrug resistance. MBio2013;4: e00273-13.
  • Quan S, Venter H, Dabbs ER.Ribosylative inactivation of rifampin by Mycobacterium smegmatis is a principal contributor to its low susceptibility to this antibiotic. Antimicrob Agents Chemother1997;41: 2456–2460.
  • Adams KN, Takaki K, Connolly LE et al.Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell2011;145: 39–53.
  • Fange D, Nilsson K, Tenson T, Ehrenberg M.Drug efflux pump deficiency and drug target resistance masking in growing bacteria. Proc Natl Acad Sci USA2009;106: 8215–8220.
  • Bhat J, Narayan A, Venkatraman J, Chatterji M.LC-MS based assay to measure intracellular compound levels in Mycobacterium smegmatis: Linking compound levels to cellular potency. J Microbiol Methods2013;94: 152–158.
  • Wood R, Lawn SD, Johnstone-Robertson S, Bekker LG.Tuberculosis control has failed in South Africa—time to reappraise strategy. S Afr Med J2011;101: 111–114.

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