Smith R, Coast J. The true cost of antimicrobial resistance. BMJ. 2013;346:f1493.
Laxminarayan R, Matsoso P, Pant S, Brower C, Røttingen J-A, Klugman K, et al. Access to effective antimicrobials: a worldwide challenge. Lancet. 2016;387:168–75.
Bergstrom CT, Lo M, Lipsitch M. Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals. Proc Natl Acad Sci U S A. 2004;101:13285–90.
Bonhoeffer S, Lipsitch M, Levin BR. Evaluating treatment protocols to prevent antibiotic resistance. Proc Natl Acad Sci U S A. 1997;94:12106–11.
Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. Int J Tuberc Lung Dis. 1999;3:S231–79.
Götte M. The distinct contributions of fitness and genetic barrier to the development of antiviral drug resistance. Curr Opin Virol. 2012;2:644–50.
Wiesch zur PA, Kouyos R, Engelstädter J, Regoes RR, Bonhoeffer S. Population biological principles of drug-resistance evolution in infectious diseases. Lancet Infect Dis. 2011;11:236–47.
Zumla A, Abubakar I, Raviglione M, Hoelscher M, Ditiu L, McHugh TD, et al. Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs. J Infect Dis. 2012;205:S228–40.
Gupta RK, Jordan MR, Sultan BJ, Hill A, Davis DHJ, Gregson J, et al. Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis. Lancet. 2012;380:1250–8.
Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13:714–26.
Torella JP, Chait R, Kishony R. Optimal drug synergy in antimicrobial treatments. PLoS Comput Biol. 2010;6:e1000796.
Hastings IM, Watkins WM, White NJ. The evolution of drug-resistant malaria: the role of drug elimination half-life. Philos Trans R Soc B. 2002;357:505–19.
Prideaux B, Via LE, Zimmerman MD, Eum S, Sarathy J, O’Brien P, et al. The association between sterilizing activity and drug distribution into tuberculosis lesions. Nat Med. 2015;21:1223–7.
Lin PL, Ford CB, Coleman MT, Myers AJ, Gawande R, Ioerger T, et al. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nat Med. 2013;20:75–9.
Laserson KF, Kenyon AS, Kenyon TA, Layloff T, Binkin NJ. Substandard tuberculosis drugs on the global market and their simple detection. Int J Tuberc Lung Dis. 2001;5:448–54.
Ford CB, Shah RR, Maeda MK, Gagneux S, Murray MB, Cohen T, et al. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat Genet. 2013;45:784–90.
Simen BB, Simons JF, Hullsiek KH, Novak RM, MacArthur RD, Baxter JD, et al. Low-abundance drug-resistant viral variants in chronically HIV-infected, antiretroviral treatment–naive patients significantly impact treatment outcomes. J Infect Dis. 2009;199:693–701.
Mitchison DA. How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. Int J Tuberc Lung Dis. 1998;2:10–5.
Pasipanodya JG, Srivastava S, Gumbo T. Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy. Clin Infect Dis. 2012;55:169–77.
Moreno-Gamez S, Hill AL, Rosenbloom DIS, Petrov DA, Nowak MA, Pennings PS. Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance. Proc Natl Acad Sci U S A. 2015;112:E2874–83.
Hegreness M, Shoresh N, Damian D, Hartl D, Kishony R. Accelerated evolution of resistance in multidrug environments. Proc Natl Acad Sci U S A. 2008;105:13977–81.
Bozic I, Reiter JG, Allen B, Antal T, Chatterjee K, Shah P, et al. Evolutionary dynamics of cancer in response to targeted combination therapy. elife. 2013;2:e00747.
Müller B, Chihota VN, Pillay M, Klopper M, Streicher EM, Coetzee G, et al. Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa. PLoS One. 2013;8:e70919.
Metcalf CJE, Birger RB, Funk S, Kouyos RD, Lloyd-Smith JO, Jansen VAA. Five challenges in evolution and infectious diseases. Epidemics. 2015;10:40–4.
Gog JR, Pellis L, Wood JLN, McLean AR, Arinaminpathy N, Lloyd-Smith JO. Seven challenges in modeling pathogen dynamics within-host and across scales. Epidemics. 2015;10:45–8.
World Health Organization. Global tuberculosis report 2015. Geneva; 2015
Chien JY, Lai CC, Tan CK, Chien ST, Yu CJ, Hsueh PR. Decline in rates of acquired multidrug-resistant tuberculosis after implementation of the directly observed therapy, short course (DOTS) and DOTS-Plus programmes in Taiwan. J Antimicrob Chemother. 2013;68:1910–6.
Weis SE, Slocum PC, Blais FX, King B, Nunn M, Matney GB, et al. The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med. 1994;330:1179–84.
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.
Dye C. Doomsday postponed? Preventing and reversing epidemics of drug-resistant tuberculosis. Nat Rev Microbiol. 2009;7:81–7.
Eldholm V, Balloux F. Antimicrobial resistance in Mycobacterium tuberculosis: the odd one out. Trends Microbiol. 2016;24:637–48.
Müller B, Borrell S, Rose G, Gagneux S. The heterogeneous evolution of multidrug-resistant Mycobacterium tuberculosis. Trends Genet. 2013;29:160–9.
Cohen KA, Abeel T, Manson McGuire A, Desjardins CA, Munsamy V, Shea TP, et al. Evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of Mycobacterium tuberculosis isolates from KwaZulu-Natal. PLoS Med. 2015;12:e1001880.
Eldholm V, Monteserin J, Rieux A, Lopez B, Sobkowiak B, Ritacco V, et al. Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain. Nat Commun. 2015;6:7119.
Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois A-C, Khim N, et al. A molecular marker of artemisinin- resistant Plasmodium falciparum malaria. Nature. 2013;505:50–5.
Andries K, Verhasselt P, Guillemont J, Göhlmann HWH, Neefs J-M, Winkler H, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005;307:223–7.
Park DJ, Lukens AK, Neafsey DE, Schaffner SF, Chang H-H, Valim C, et al. Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite. Proc Natl Acad Sci U S A. 2012;109:13052–7.
Zhang H, Li D, Zhao L, Fleming J, Lin N, Wang T, et al. Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat Genet. 2013;45:1255–60.
Farhat MR, Shapiro BJ, Kieser KJ, Sultana R, Jacobson KR, Victor TC, et al. Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat Genet. 2013;45:1183–9.
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. 2011;44:106–10.
Bloemberg GV, Keller PM, Stucki D, Stuckia D, Trauner A, Borrell S, et al. Acquired resistance to bedaquiline and delamanid in therapy for tuberculosis. N Engl J Med. 2015;373:1986–8.
Sun G, Luo T, Yang C, Dong X, Li J, Zhu Y, et al. Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. J Infect Dis. 2012;206:1724–33.
Eldholm V, Norheim G, Lippe Von Der B, Kinander W, Dahle UR, Caugant DA, et al. Evolution of extensively drug-resistant Mycobacterium tuberculosis from a susceptible ancestor in a single patient. Genome Biol. 2014;15:490.
Engle EK, Fisher DAC, Miller CA, McLellan MD, Fulton RS, Moore DM, et al. Clonal evolution revealed by whole genome sequencing in a case of primary myelofibrosis transformed to secondary acute myeloid leukemia. Leukemia. 2015;29:869–76.
Ford CB, Funt JM, Abbey D, Issi L, Guiducci C, Martinez DA, et al. The evolution of drug resistance in clinical isolates of Candida albicans. elife. 2015;4:e00662.
Hopewell PC, Fair EL, Uplekar M. Updating the international standards for tuberculosis care. Entering the era of molecular diagnostics. Ann Am Thorac Soc. 2014;11:277–85.
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;167:603–62.
Domenech P, Kolly GS, Leon-Solis L, Fallow A, Reed MB. Massive gene duplication event among clinical isolates of the Mycobacterium tuberculosis W/Beijing family. J Bacteriol. 2010;192:4562–70.
Weiner B, Gomez J, Victor TC, Warren RM, Sloutsky A, Plikaytis BB, et al. Independent large scale duplications in multiple M. tuberculosis lineages overlapping the same genomic region. PLoS One. 2012;7:e26038.
Liu Q, Via LE, Luo T, Liang L, Liu X, Wu S, et al. Within patient microevolution of Mycobacterium tuberculosis correlates with heterogeneous responses to treatment. Sci Rep. 2015;5:17507.
Lenaerts A, Barry CE, Dartois V. Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses. Immunol Rev. 2015;264:288–307.
Hartkoorn RC, Uplekar S, Cole ST. Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2014;58:2979–81.
Pethe K, Sequeira PC, Agarwalla S, Rhee K, Kuhen K, Phong WY, et al. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat Commun. 2010;1:1–8.
Black PA, de Vos M, Louw GE, van der Merwe RG, Dippenaar A, Streicher EM, et al. Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates. BMC Genomics. 2015;16:857.
O’Neill MB, Mortimer TD, Pepperell CS. Diversity of Mycobacterium tuberculosis across evolutionary scales. PLoS Pathog. 2015;11:e1005257.
Lieberman TD, Wilson D, Misra R, Xiong LL, Moodley P, Cohen T, et al. Genomic diversity in autopsy samples reveals within-host dissemination of HIV-associated Mycobacterium tuberculosis. Nat Med. 2016;22:1470–4.
Pepperell CS, Casto AM, Kitchen A, Granka JM, Cornejo OE, Holmes EC, et al. The role of selection in shaping diversity of natural M. tuberculosis populations. PLoS Pathog. 2013;9:e1003543.
Lieberman TD, Flett KB, Yelin I, Martin TR, McAdam AJ, Priebe GP, et al. Genetic variation of a bacterial pathogen within individuals with cystic fibrosis provides a record of selective pressures. Nat Genet. 2014;46:82–7.
Pérez-Lago L, Comas I, Navarro Y, González-Candelas F, Herranz M, Bouza E, et al. Whole genome sequencing analysis of intrapatient microevolution in Mycobacterium tuberculosis: potential impact on the inference of tuberculosis transmission. J Infect Dis. 2014;209:98–108.
Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJM. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science. 2006;312:1944–6.
Trauner A, Borrell S, Reither K, Gagneux S. Evolution of drug resistance in tuberculosis: recent progress and implications for diagnosis and therapy. Drugs. 2014;74:1063–72.
Grandjean L, Gilman RH, Martin L, Soto E, Castro B, Lopez S, et al. Transmission of multidrug-resistant and drug-susceptible tuberculosis within households: a prospective cohort study. PLoS Med. 2015;12:e1001843.
Andersson DI, Hughes D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol. 2010;8:260–71.
Hurst LD. Fundamental concepts in genetics: genetics and the understanding of selection. Nat Rev Genet. 2009;10:83–93.
Kryazhimskiy S, Plotkin JB. The population genetics of dN/dS. PLoS Genet. 2008;4:e1000304.
Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S, Homolka S, et al. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol. 2008;6:e311.
Comas I, Chakravartti J, Small PM, Galagan J, Niemann S, Kremer K, et al. Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat Genet. 2010;42:498–503.
Sampson SL. Strength in Diversity: Hidden genetic depths of Mycobacterium tuberculosis. Trends Microbiol. 2016;24:82–4.
Palmer AC, Kishony R. Understanding, predicting and manipulating the genotypic evolution of antibiotic resistance. Nat Rev Genet. 2013;14:243–8.
Merker M, Kohl TA, Roetzer A, Truebe L, Richter E, Rüsch-Gerdes S, et al. Whole genome sequencing reveals complex evolution patterns of multidrug-resistant Mycobacterium tuberculosis Beijing strains in patients. PLoS One. 2013;8:e82551.
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.
Whitlock MC. Fixation probability and time in subdivided populations. Genetics. 2003;164:767–79.
Walker TM, Kohl TA, Omar SV, Hedge J, Del Ojo EC, Bradley P, et al. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect Dis. 2015;15:1193–202.
Coscollà M, Copin R, Sutherland J, Gehre F, de Jong B, Owolabi O, et al. M. tuberculosis T cell epitope analysis reveals paucity of antigenic variation and identifies rare variable TB antigens. Cell Host Microbe. 2015;18:538–48.
Charlesworth B. The effects of deleterious mutations on evolution at linked sites. Genetics. 2012;190:5–22.
Stephan W. Genetic hitchhiking versus background selection: the controversy and its implications. Philos Trans R Soc B. 2010;365:1245–53.
Brites D, Gagneux S. Co-evolution of Mycobacterium tuberculosis and Homo sapiens. Immunol Rev. 2015;264:6–24.
Lieberman TD, Michel J-B, Aingaran M, Potter-Bynoe G, Roux D, Davis MR, et al. Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes. Nat Genet. 2011;43:1275–80.
Marvig RL, Sommer LM, Molin S, Johansen HK. Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis. Nat Genet. 2014;47:57–64.
Jorth P, Staudinger BJ, Wu X, Hisert KB, Hayden H, Garudathri J, et al. Regional isolation drives bacterial diversification within cystic fibrosis lungs. Cell Host Microbe. 2015;18:307–19.
Kennemann L, Didelot X, Aebischer T, Kuhn S, Drescher B, Droege M, et al. Helicobacter pylori genome evolution during human infection. Proc Natl Acad Sci U S A. 2011;108:5033–8.
Golubchik T, Batty EM, Miller RR, Farr H, Young BC, Larner-Svensson H, et al. Within-host evolution of Staphylococcus aureus during asymptomatic carriage. PLoS One. 2013;8:e61319.
Stucki D, Brites D, Jeljeli L, Coscollà M, Liu Q, Trauner A, et al. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nat Genet. 2016;48:1535–43.
Smith NH, Gordon SV, La Rua-Domenech de R, Clifton-Hadley RS, Hewinson RG. Bottlenecks and broomsticks: the molecular evolution of Mycobacterium bovis. Nat Rev Microbiol. 2006;4:670–81.
Huang W, Li L, Myers JR, Marth GT. ART: a next-generation sequencing read simulator. Bioinformatics. 2012;28:593–4.
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60.
Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25:2078–9.
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;393:537–44.
Zhang Y, Chen C, Liu J, Deng H, Pan A, Zhang L, et al. Complete genome sequences of Mycobacterium tuberculosis strains CCDC5079 and CCDC5080, which belong to the Beijing family. J Bacteriol. 2011;193:5591–2.
Wilm A, Aw PPK, Bertrand D, Yeo GHT, Ong SH, Wong CH, et al. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets. Nucleic Acids Res. 2012;40:11189–201.
Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD, Lin L, et al. VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 2012;22:568–76.
Van Der Walt S, Colbert SC, Varoquaux G. The NumPy array: a structure for efficient numerical computation. Comput Sci Eng. 2011;13:22–30. Available from: https://arxiv.org/abs/1102.1523.
McKinney W. Data structures for statistical computing in Python. Proceedings of the 9th Python in Science Conference. 2010. p. 51–6. Available from: http://conference.scipy.org/proceedings/scipy2010/pdfs/mckinney.pdf.
Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, et al. Scikit-learn: Machine learning in Python. Machine Learn Res. 2011;12:2825–30.
Pérez F, Granger BE. IPython: a system for interactive scientific computing. Comput Sci Eng. 2007;9:21–9.
Hunter JD. Matplotlib: a 2D graphics environment. Comput Sci Eng. 2007;9:90–5. Available from: http://ieeexplore.ieee.org/document/4160265/.
Seabold S, Perktold J. Statsmodels: Econometric and statistical modeling with python. Proceedings of the 9th Python in Science Conference. 2010. p. 57–61. Available from: http://conference.scipy.org/proceedings/scipy2010/pdfs/seabold.pdf.
Hasegawa M, Kishino H, Yano T. Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol. 1985;22:160–74.