The ability to predict the evolutionary trajectories of antibiotic resistance would be of great value in tailoring dosing regimens of antibiotics so as to maximize the duration of their usefulness. Useful prediction of resistance evolution requires information about () the mutation supply rate, () the level of resistance conferred by the resistance mechanism, () the fitness of the antibiotic-resistant mutant bacteria as a function of drug concentration, and () the strength of selective pressures. In addition, processes including epistatic interactions and compensatory evolution, coselection of drug resistances, and population bottlenecks and clonal interference can strongly influence resistance evolution and thereby complicate attempts at prediction. Currently, the very limited quantitative data on most of these parameters severely limit attempts to accurately predict trajectories of resistance evolution.


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Literature Cited

  1. Abdulkarim F, Hughes D. 1.  1996. Homologous recombination between the tuf genes of Salmonella typhimurium. J. Mol. Biol. 260:506–22 [Google Scholar]
  2. Alekshun MN, Levy SB. 2.  2007. Molecular mechanisms of antibacterial multidrug resistance. Cell 128:1037–50 [Google Scholar]
  3. Anderson P, Roth J. 3.  1981. Spontaneous tandem genetic duplications in Salmonella typhimurium arise by unequal recombination between rRNA (rrn) cistrons. PNAS 78:3113–17 [Google Scholar]
  4. Andersson DI. 4.  2015. Improving predictions of the risk of resistance development against new and old antibiotics. Clin. Microbiol. Infect. Dis. 21:894–98 [Google Scholar]
  5. Andersson DI, Hughes D. 5.  1996. Muller's ratchet decreases fitness of a DNA-based microbe. PNAS 93:906–7 [Google Scholar]
  6. Andersson DI, Hughes D. 6.  2010. Antibiotic resistance and its cost: Is it possible to reverse resistance?. Nat. Rev. Microbiol. 8:260–71 [Google Scholar]
  7. Andersson DI, Hughes D. 7.  2014. Microbiological effects of sublethal levels of antibiotics. Nat. Rev. Microbiol. 12:465–78 [Google Scholar]
  8. Andersson DI, Hughes D, Roth JR. 8.  2013. The origin of mutants under selection: interactions of mutation, growth, and selection. EcoSal Plus 4:2 https://doi.org/10.1128/ecosalplus.5.6.6 [Crossref] [Google Scholar]
  9. Andersson DI, Levin BR. 9.  1999. The biological cost of antibiotic resistance. Curr. Opin. Microbiol. 2:489–93 [Google Scholar]
  10. Angst DC, Hall AR. 10.  2013. The cost of antibiotic resistance depends on evolutionary history in Escherichia coli. BMC Evol. Biol. 13:163 [Google Scholar]
  11. Banerjee R, Johnson JR. 11.  2014. A new clone sweeps clean: the enigmatic emergence of Escherichia coli sequence type 131. Antimicrob. Agents Chemother. 58:4997–5004 [Google Scholar]
  12. Banos RC, Vivero A, Aznar S, Garcia J, Pons M. 12.  et al. 2009. Differential regulation of horizontally acquired and core genome genes by the bacterial modulator H-NS. PLOS Genet 5:e1000513 [Google Scholar]
  13. Bean DC, Livermore DM, Papa I, Hall LM. 13.  2005. Resistance among Escherichia coli to sulphonamides and other antimicrobials now little used in man. J. Antimicrob. Chemother. 56:962–64 [Google Scholar]
  14. Bedhomme S, Hillung J, Elena SF. 14.  2015. Emerging viruses: why they are not jack of all trades?. Curr. Opin. Virol. 10:1–6 [Google Scholar]
  15. Bingen E, Lambert-Zechovsky N, Mariani-Kurkdjian P, Doit C, Aujard Y. 15.  et al. 1990. Bacterial counts in cerebrospinal fluid of children with meningitis. Eur. J. Clin. Microbiol. Infect. Dis. 9:278–81 [Google Scholar]
  16. Bjorkman J, Hughes D, Andersson DI. 16.  1998. Virulence of antibiotic-resistant Salmonella typhimurium. PNAS 95:3949–53 [Google Scholar]
  17. Bjorkman J, Samuelsson P, Andersson DI, Hughes D. 17.  1999. Novel ribosomal mutations affecting translational accuracy, antibiotic resistance and virulence of Salmonella typhimurium. Mol. Microbiol. 31:53–58 [Google Scholar]
  18. Bottger EC, Springer B, Pletschette M, Sander P. 18.  1998. Fitness of antibiotic-resistant microorganisms and compensatory mutations. Nat. Med. 4:1343–44 [Google Scholar]
  19. Brandis G, Hughes D. 19.  2013. Genetic characterization of compensatory evolution in strains carrying rpoB Ser531Leu, the rifampicin resistance mutation most frequently found in clinical isolates. J. Antimicrob. Chemother. 68:2493–97 [Google Scholar]
  20. Brandis G, Pietsch F, Alemayehu R, Hughes D. 20.  2015. Comprehensive phenotypic characterization of rifampicin resistance mutations in Salmonella provides insight into the evolution of resistance in Mycobacterium tuberculosis. J. Antimicrob. Chemother. 70:680–85 [Google Scholar]
  21. Brandis G, Wrande M, Liljas L, Hughes D. 21.  2012. Fitness-compensatory mutations in rifampicin-resistant RNA polymerase. Mol. Microbiol. 85:142–51 [Google Scholar]
  22. Brolund A, Sandegren L. 22.  2016. Characterization of ESBL disseminating plasmids. Infect Dis 48:18–25 [Google Scholar]
  23. Cabezon E, Ripoll-Rozada J, Pena A, de la Cruz F, Arechaga I. 23.  2015. Towards an integrated model of bacterial conjugation. FEMS Microbiol. Rev. 39:81–95 [Google Scholar]
  24. Cambray G, Guerout AM, Mazel D. 24.  2010. Integrons. Annu. Rev. Genet. 44:141–66 [Google Scholar]
  25. Canetti G. 25.  1956. Dynamic aspects of the pathology and bacteriology of tuberculous lesions. Am. Rev. Tuberc. 74:13–21; discussion 22–27 [Google Scholar]
  26. Canetti G. 26.  1965. Present aspects of bacterial resistance in tuberculosis. Am. Rev. Respir. Dis. 92:687–703 [Google Scholar]
  27. Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. 27.  2014. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol 22:686–96 [Google Scholar]
  28. Chen L, Mathema B, Pitout JD, DeLeo FR, Kreiswirth BN. 28.  2014. Epidemic Klebsiella pneumoniae ST258 is a hybrid strain. mBio 5:e01355–14 [Google Scholar]
  29. Chevereau G, Dravecka M, Batur T, Guvenek A, Ayhan DH. 29.  et al. 2015. Quantifying the determinants of evolutionary dynamics leading to drug resistance. PLOS Biol 13:e1002299 [Google Scholar]
  30. Clancy CJ, Chen L, Hong JH, Cheng S, Hao B. 30.  et al. 2013. Mutations of the ompK36 porin gene and promoter impact responses of sequence type 258, KPC-2-producing Klebsiella pneumoniae strains to doripenem and doripenem-colistin. Antimicrob. Agents Chemother 57:5258–65 [Google Scholar]
  31. Coque TM, Novais A, Carattoli A, Poirel L, Pitout J. 31.  et al. 2008. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum beta-lactamase CTX-M-15. Emerg. Infect. Dis. 14:195–200 [Google Scholar]
  32. Dahlberg C, Chao L. 32.  2003. Amelioration of the cost of conjugative plasmid carriage in Escherichia coli K12. Genetics 165:1641–49 [Google Scholar]
  33. D'Costa VM, McGrann KM, Hughes DW, Wright GD. 33.  2006. Sampling the antibiotic resistome. Science 311:374–77 [Google Scholar]
  34. de Visser JA, Krug J. 34.  2014. Empirical fitness landscapes and the predictability of evolution. Nat. Rev. Genet. 15:480–90 [Google Scholar]
  35. Denamur E, Bonacorsi S, Giraud A, Duriez P, Hilali F. 35.  et al. 2002. High frequency of mutator strains among human uropathogenic Escherichia coli isolates. J. Bacteriol. 184:605–9 [Google Scholar]
  36. Drake JW. 36.  1999. The distribution of rates of spontaneous mutation over viruses, prokaryotes, and eukaryotes. Ann. N. Y. Acad. Sci. 870:100–7 [Google Scholar]
  37. Drake JW, Charlesworth B, Charlesworth D, Crow JF. 37.  1998. Rates of spontaneous mutation. Genetics 148:1667–86 [Google Scholar]
  38. Dunny G, Yuhasz M, Ehrenfeld E. 38.  1982. Genetic and physiological analysis of conjugation in Streptococcus faecalis. J. Bacteriol. 151:855–59 [Google Scholar]
  39. Enne VI, Livermore DM, Stephens P, Hall LM. 39.  2001. Persistence of sulphonamide resistance in Escherichia coli in the UK despite national prescribing restriction. Lancet 357:1325–8 [Google Scholar]
  40. Feldman WE. 40.  1976. Concentrations of bacteria in cerebrospinal fluid of patients with bacterial meningitis. J. Pediatr. 88:549–52 [Google Scholar]
  41. Foster PL. 41.  2006. Methods for determining spontaneous mutation rates. Methods Enzymol 409:195–213 [Google Scholar]
  42. Garcia LG, Lemaire S, Kahl BC, Becker K, Proctor RA. 42.  et al. 2013. Antibiotic activity against small-colony variants of Staphylococcus aureus: review of in vitro, animal and clinical data. J. Antimicrob. Chemother. 68:1455–64 [Google Scholar]
  43. Gerrish PJ, Lenski RE. 43.  1998. The fate of competing beneficial mutations in an asexual population. Genetica 102–103:127–44 [Google Scholar]
  44. Gifford DR, MacLean RC. 44.  2013. Evolutionary reversals of antibiotic resistance in experimental populations of Pseudomonas aeruginosa. Evolution 67:2973–81 [Google Scholar]
  45. Gorini L. 45.  1970. Informational suppression. Annu. Rev. Genet. 4:107–34 [Google Scholar]
  46. Gullberg E, Albrecht LM, Karlsson C, Sandegren L, Andersson DI. 46.  2014. Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals. mBio 5:e01918–14 [Google Scholar]
  47. Gullberg E, Cao S, Berg OG, Ilback C, Sandegren L. 47.  et al. 2011. Selection of resistant bacteria at very low antibiotic concentrations. PLOS Pathog 7:e1002158 [Google Scholar]
  48. Gwynn MN, Portnoy A, Rittenhouse SF, Payne DJ. 48.  2010. Challenges of antibacterial discovery revisited. Ann. N. Y. Acad. Sci. 1213:5–19 [Google Scholar]
  49. Hall AR, MacLean RC. 49.  2011. Epistasis buffers the fitness effects of rifampicin-resistance mutations in Pseudomonas aeruginosa. Evolution 65:2370–79 [Google Scholar]
  50. Hilty M, Betsch BY, Bogli-Stuber K, Heiniger N, Stadler M. 50.  et al. 2012. Transmission dynamics of extended-spectrum β-lactamase–producing Enterobacteriaceae in the tertiary care hospital and the household setting. Clin. Infect. Dis. 55:967–75 [Google Scholar]
  51. Hughes D, Andersson DI. 51.  2015. Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms. Nat. Rev. Genet. 16:459–71 [Google Scholar]
  52. Hughes D, Andersson DI. 52.  2017. Environmental and genetic modulation of the phenotypic expression of antibiotic resistance. FEMS Microbiol. Rev. 41:374–91 [Google Scholar]
  53. Hughes JM, Lohman BK, Deckert GE, Nichols EP, Settles M. 53.  et al. 2012. The role of clonal interference in the evolutionary dynamics of plasmid-host adaptation. mBio 3:e00077–12 [Google Scholar]
  54. Huseby DL, Pietsch F, Brandis G, Garoff L, Tegehall A, Hughes D. 54.  2017. Mutation supply and relative fitness shape the genotypes of ciprofloxacin-resistant Escherichia coli. Mol. Biol. Evol. 34:1029–39 [Google Scholar]
  55. Imamovic L, Sommer MO. 55.  2013. Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development. Sci. Transl. Med. 5:204ra132 [Google Scholar]
  56. Johanson U, Aevarsson A, Liljas A, Hughes D. 56.  1996. The dynamic structure of EF-G studied by fusidic acid resistance and internal revertants. J. Mol. Biol. 258:420–32 [Google Scholar]
  57. Johnson JR, Miller S, Johnston B, Clabots C, Debroy C. 57.  2009. Sharing of Escherichia coli sequence type ST131 and other multidrug-resistant and urovirulent E. coli strains among dogs and cats within a household. J. Clin. Microbiol 47:3721–25 [Google Scholar]
  58. Johnson JR, Tchesnokova V, Johnston B, Clabots C, Roberts PL. 58.  et al. 2013. Abrupt emergence of a single dominant multidrug-resistant strain of Escherichia coli. J. Infect. Dis. 207:919–28 [Google Scholar]
  59. Kim S, Lieberman TD, Kishony R. 59.  2014. Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance. PNAS 111:14494–99 [Google Scholar]
  60. Komp Lindgren P, Marcusson LL, Sandvang D, Frimodt-Moller N, Hughes D. 60.  2005. Biological cost of single and multiple norfloxacin resistance mutations in Escherichia coli implicated in urinary tract infections. Antimicrob. Agents Chemother. 49:2343–51 [Google Scholar]
  61. Kondrashov DA, Kondrashov FA. 61.  2015. Topological features of rugged fitness landscapes in sequence space. Trends Genet 31:24–33 [Google Scholar]
  62. Kubicek-Sutherland JZ, Heithoff DM, Ersoy SC, Shimp WR, House JK. 62.  et al. 2015. Host-dependent induction of transient antibiotic resistance: a prelude to treatment failure. EBioMedicine 2:1169–78 [Google Scholar]
  63. Lannergard J, Cao S, Norstrom T, Delgado A, Gustafson JE, Hughes D. 63.  2011. Genetic complexity of fusidic acid-resistant small colony variants (SCV) in Staphylococcus aureus. PLOS ONE 6:e28366 [Google Scholar]
  64. Lazar V, Nagy I, Spohn R, Csorgo B, Gyorkei A. 64.  et al. 2014. Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network. Nat. Commun. 5:4352 [Google Scholar]
  65. LeClerc JE, Li B, Payne WL, Cebula TA. 65.  1996. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 274:1208–11 [Google Scholar]
  66. Lee Y, Kim BS, Chun J, Yong JH, Lee YS. 66.  et al. 2014. Clonality and resistome analysis of KPC-producing Klebsiella pneumoniae strain isolated in Korea using whole genome sequencing. Biomed. Res. Int 2014:352862 [Google Scholar]
  67. Leekitcharoenphon P, Hendriksen RS, Le Hello S, Weill FX, Baggesen DL. 67.  et al. 2016. Global genomic epidemiology of Salmonella enterica serovar Typhimurium DT104. Appl. Environ. Microbiol. 82:2516–26 [Google Scholar]
  68. Locke JB, Hilgers M, Shaw KJ. 68.  2009. Novel ribosomal mutations in Staphylococcus aureus strains identified through selection with the oxazolidinones linezolid and torezolid (TR-700). Antimicrob. Agents Chemother. 53:5265–74 [Google Scholar]
  69. Loftie-Eaton W, Yano H, Burleigh S, Simmons RS, Hughes JM. 69.  et al. 2016. Evolutionary paths that expand plasmid host-range: implications for spread of antibiotic resistance. Mol. Biol. Evol. 33:885–97 [Google Scholar]
  70. Lofton H, Pranting M, Thulin E, Andersson DI. 70.  2013. Mechanisms and fitness costs of resistance to antimicrobial peptides LL-37, CNY100HL and wheat germ histones. PLOS ONE 8:e68875 [Google Scholar]
  71. Lynch M. 71.  2010. Evolution of the mutation rate. Trends Genet 26:345–52 [Google Scholar]
  72. Macvanin M, Hughes D. 72.  2005. Hyper-susceptibility of a fusidic acid-resistant mutant of Salmonella to different classes of antibiotics. FEMS Microbiol. Lett. 247:215–20 [Google Scholar]
  73. Maisnier-Patin S, Berg OG, Liljas L, Andersson DI. 73.  2002. Compensatory adaptation to the deleterious effect of antibiotic resistance in Salmonella typhimurium. Mol. Microbiol. 46:355–66 [Google Scholar]
  74. Marcusson LL, Frimodt-Moller N, Hughes D. 74.  2009. Interplay in the selection of fluoroquinolone resistance and bacterial fitness. PLOS Pathog 5:e1000541 [Google Scholar]
  75. Mariam SH, Werngren J, Aronsson J, Hoffner S, Andersson DI. 75.  2011. Dynamics of antibiotic resistant Mycobacterium tuberculosis during long-term infection and antibiotic treatment. PLOS ONE 6:e21147 [Google Scholar]
  76. Markussen T, Marvig RL, Gomez-Lozano M, Aanaes K, Burleigh AE. 76.  et al. 2014. Environmental heterogeneity drives within-host diversification and evolution of Pseudomonas aeruginosa. mBio 5:e01592–14 [Google Scholar]
  77. Mathers AJ, Peirano G, Pitout JD. 77.  2015. Escherichia coli ST131: the quintessential example of an international multiresistant high-risk clone. Adv. Appl. Microbiol. 90:109–54 [Google Scholar]
  78. Mathers AJ, Peirano G, Pitout JD. 78.  2015. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin. Microbiol. Rev. 28:565–91 [Google Scholar]
  79. Molton JS, Tambyah PA, Ang BS, Ling ML, Fisher DA. 79.  2013. The global spread of healthcare-associated multidrug-resistant bacteria: a perspective from Asia. Clin. Infect. Dis. 56:1310–18 [Google Scholar]
  80. Nagaev I, Bjorkman J, Andersson DI, Hughes D. 80.  2001. Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus. Mol. Microbiol. 40:433–39 [Google Scholar]
  81. Nicolas-Chanoine MH, Blanco J, Leflon-Guibout V, Demarty R, Alonso MP. 81.  et al. 2008. Intercontinental emergence of Escherichia coli clone O25: H4-ST131 producing CTX-M-15. J. Antimicrob. Chemother. 61:273–81 [Google Scholar]
  82. Nilsson AI, Berg OG, Aspevall O, Kahlmeter G, Andersson DI. 82.  2003. Biological costs and mechanisms of fosfomycin resistance in Escherichia coli. Antimicrob. Agents Chemother. 47:2850–58 [Google Scholar]
  83. Nishino K, Hayashi-Nishino M, Yamaguchi A. 83.  2009. H-NS modulates multidrug resistance of Salmonella enterica serovar Typhimurium by repressing multidrug efflux genes acrEF. Antimicrob. Agents Chemother. 53:3541–43 [Google Scholar]
  84. Oethinger M, Kern WV, Jellen-Ritter AS, McMurry LM, Levy SB. 84.  2000. Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump. Antimicrob. Agents Chemother. 44:10–13 [Google Scholar]
  85. Oliver A, Canton R, Campo P, Baquero F, Blazquez J. 85.  2000. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–54 [Google Scholar]
  86. Oliver A, Mulet X, Lopez-Causape C, Juan C. 86.  2015. The increasing threat of Pseudomonas aeruginosa high-risk clones. Drug Resist. Updates 21–22:41–59 [Google Scholar]
  87. O'Neill AJ, Huovinen T, Fishwick CW, Chopra I. 87.  2006. Molecular genetic and structural modeling studies of Staphylococcus aureus RNA polymerase and the fitness of rifampin resistance genotypes in relation to clinical prevalence. Antimicrob. Agents Chemother. 50:298–309 [Google Scholar]
  88. Oz T, Guvenek A, Yildiz S, Karaboga E, Tamer YT. 88.  et al. 2014. Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution. Mol. Biol. Evol. 31:2387–401 [Google Scholar]
  89. Palaci M, Dietze R, Hadad DJ, Ribeiro FK, Peres RL. 89.  et al. 2007. Cavitary disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J. Clin. Microbiol. 45:4064–66 [Google Scholar]
  90. Palmer AC, Kishony R. 90.  2013. Understanding, predicting and manipulating the genotypic evolution of antibiotic resistance. Nat. Rev. Genet. 14:243–48 [Google Scholar]
  91. Pawlowski AC, Wang W, Koteva K, Barton HA, McArthur AG, Wright GD. 91.  2016. A diverse intrinsic antibiotic resistome from a cave bacterium. Nat. Commun. 7:13803 [Google Scholar]
  92. Pena-Miller R, Laehnemann D, Jansen G, Fuentes-Hernandez A, Rosenstiel P. 92.  et al. 2013. When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition. PLOS Biol 11:e1001540 [Google Scholar]
  93. Perichon B, Courvalin P. 93.  2006. Synergism between β-lactams and glycopeptides against VanA-type methicillin-resistant Staphylococcus aureus and heterologous expression of the vanA operon. Antimicrob. Agents Chemother 50:3622–30 [Google Scholar]
  94. Price LB, Johnson JR, Aziz M, Clabots C, Johnston B. 94.  et al. 2013. The epidemic of extended-spectrum-β-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. mBio 4:e00377–13 [Google Scholar]
  95. Reams AB, Kofoid E, Kugelberg E, Roth JR. 95.  2012. Multiple pathways of duplication formation with and without recombination (RecA) in Salmonella enterica. Genetics 192:397–415 [Google Scholar]
  96. Reams AB, Kofoid E, Savageau M, Roth JR. 96.  2010. Duplication frequency in a population of Salmonella enterica rapidly approaches steady state with or without recombination. Genetics 184:1077–94 [Google Scholar]
  97. Roberts AP, Mullany P. 97.  2011. Tn916-like genetic elements: a diverse group of modular mobile elements conferring antibiotic resistance. FEMS Microbiol. Rev. 35:856–71 [Google Scholar]
  98. Roth JR. 98.  1981. Frameshift suppression. Cell 24:601–2 [Google Scholar]
  99. Rozen DE, McGee L, Levin BR, Klugman KP. 99.  2007. Fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 51:412–16 [Google Scholar]
  100. Salverda ML, Dellus E, Gorter FA, Debets AJ, van der Oost J. 100.  et al. 2011. Initial mutations direct alternative pathways of protein evolution. PLOS Genet 7:e1001321 [Google Scholar]
  101. San Millan A, Heilbron K, MacLean RC. 101.  2014. Positive epistasis between co-infecting plasmids promotes plasmid survival in bacterial populations. ISME J 8:601–12 [Google Scholar]
  102. San Millan A, Pena-Miller R, Toll-Riera M, Halbert ZV, McLean AR. 102.  et al. 2014. Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids. Nat. Commun. 5:5208 [Google Scholar]
  103. Sander P, Springer B, Prammananan T, Sturmfels A, Kappler M. 103.  et al. 2002. Fitness cost of chromosomal drug resistance-conferring mutations. Antimicrob. Agents Chemother. 46:1204–11 [Google Scholar]
  104. Schrag SJ, Perrot V, Levin BR. 104.  1997. Adaptation to the fitness costs of antibiotic resistance in Escherichia coli. Proc. Biol. Sci. 264:1287–91 [Google Scholar]
  105. Shcherbakov D, Akbergenov R, Matt T, Sander P, Andersson DI, Bottger EC. 105.  2010. Directed mutagenesis of Mycobacterium smegmatis 16S rRNA to reconstruct the in-vivo evolution of aminoglycoside resistance in Mycobacterium tuberculosis. Mol. Microbiol. 77:830–40 [Google Scholar]
  106. Silva RF, Mendonca SC, Carvalho LM, Reis AM, Gordo I. 106.  et al. 2011. Pervasive sign epistasis between conjugative plasmids and drug-resistance chromosomal mutations. PLOS Genet 7:e1002181 [Google Scholar]
  107. Silver LL. 107.  2011. Challenges of antibacterial discovery. Clin. Microbiol. Rev. 24:71–109 [Google Scholar]
  108. Smith MR, Wood WB Jr.. 108.  1956. An experimental analysis of the curative action of penicillin in acute bacterial infections: III. The effect of suppuration upon the antibacterial action of the drug. J. Exp. Med. 103:509–22 [Google Scholar]
  109. Sommer MO, Dantas G, Church GM. 109.  2009. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325:1128–31 [Google Scholar]
  110. Stephan J, Mailaender C, Etienne G, Daffe M, Niederweis M. 110.  2004. Multidrug resistance of a porin deletion mutant of Mycobacterium smegmatis. Antimicrob. Agents Chemother. 48:4163–70 [Google Scholar]
  111. Suerbaum S, Josenhans C. 111.  2007. Helicobacter pylori evolution and phenotypic diversification in a changing host. Nat. Rev. Microbiol. 5:441–52 [Google Scholar]
  112. Sundqvist M, Geli P, Andersson DI, Sjolund-Karlsson M, Runehagen A. 112.  et al. 2009. Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use. J. Antimicrob. Chemother. 65:350–60 [Google Scholar]
  113. Szybalski W, Bryson V. 113.  1952. Genetic studies on microbial cross resistance to toxic agents: I. Cross resistance of Escherichia coli to fifteen antibiotics. J. Bacteriol. 64:489–99 [Google Scholar]
  114. Thulin E, Sundqvist M, Andersson DI. 114.  2015. Amdinocillin (mecillinam) resistance mutations in clinical isolates and laboratory-selected mutants of Escherichia coli. Antimicrob. Agents Chemother. 59:1718–27 [Google Scholar]
  115. Trindade S, Sousa A, Xavier KB, Dionisio F, Ferreira MG, Gordo I. 115.  2009. Positive epistasis drives the acquisition of multidrug resistance. PLOS Genet 5:e1000578 [Google Scholar]
  116. Tubulekas I, Buckingham RH, Hughes D. 116.  1991. Mutant ribosomes can generate dominant kirromycin resistance. J. Bacteriol. 173:3635–43 [Google Scholar]
  117. Villa J, Viedma E, Branas P, Mingorance J, Chaves F. 117.  2014. Draft whole-genome sequence of OXA-48-producing multidrug-resistant Klebsiella pneumoniae KP_ST11_OXA-48. Genome Announc 2:e00737–14 [Google Scholar]
  118. Villa L, Capone A, Fortini D, Dolejska M, Rodriguez I. 118.  et al. 2013. Reversion to susceptibility of a carbapenem-resistant clinical isolate of Klebsiella pneumoniae producing KPC-3. J. Antimicrob. Chemother. 68:2482–86 [Google Scholar]
  119. Vogwill T, Kojadinovic M, MacLean RC. 119.  2016. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas. Proc. Biol. Sci. 283:20160151 [Google Scholar]
  120. Vogwill T, MacLean RC. 120.  2015. The genetic basis of the fitness costs of antimicrobial resistance: a meta-analysis approach. Evol. Appl. 8:284–95 [Google Scholar]
  121. Weinreich DM, Delaney NF, Depristo MA, Hartl DL. 121.  2006. Darwinian evolution can follow only very few mutational paths to fitter proteins. Science 312:111–14 [Google Scholar]
  122. Wiser MJ, Ribeck N, Lenski RE. 122.  2013. Long-term dynamics of adaptation in asexual populations. Science 342:1364–67 [Google Scholar]
  123. Worby CJ, Lipsitch M, Hanage WP. 123.  2014. Within-host bacterial diversity hinders accurate reconstruction of transmission networks from genomic distance data. PLOS Comput. Biol. 10:e1003549 [Google Scholar]
  124. zur Wiesch PA, Kouyos R, Engelstadter J, Regoes RR, Bonhoeffer S. 124.  2011. Population biological principles of drug-resistance evolution in infectious diseases. Lancet Infect. Dis. 11:236–47 [Google Scholar]

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