1887

Abstract

The antibiotic ciprofloxacin is used extensively to treat a wide range of infections caused by the opportunistic pathogen Pseudomonas aeruginosa. Due to its extensive use, the proportion of ciprofloxacin-resistant P. aeruginosa isolates is rapidly increasing. Ciprofloxacin resistance can arise through the acquisition of mutations in genes encoding the target proteins of ciprofloxacin and regulators of efflux pumps, which leads to overexpression of these pumps. However, understanding of the basis of ciprofloxacin resistance is not yet complete. Recent advances using high-throughput screens and experimental evolution combined with whole-genome sequencing and protein analysis are enhancing our understanding of the genetic and biochemical mechanisms involved in ciprofloxacin resistance. Better insights into the mechanisms of ciprofloxacin resistance may facilitate the development of new or improved therapeutic regimes effective against P. aeruginosa. In this review we discuss the current understanding of the mechanisms of ciprofloxacin resistance and summarize the genetic basis of ciprofloxacin resistance in P. aeruginosa, in the context of current and future use of this antibiotic.

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2018-11-21
2024-11-04
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References

  1. Driscoll JA, Brody SL, Kollef MH. The epidemiology, pathogenesis and treatment of Pseudomonas aeruginosa infections. Drugs 2007; 67:351–368 [View Article][PubMed]
    [Google Scholar]
  2. Lyczak JB, Cannon CL, Pier GB. Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2000; 2:1051–1060[PubMed]
    [Google Scholar]
  3. Gaynes R, Edwards JR. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005; 41:848–854 [View Article][PubMed]
    [Google Scholar]
  4. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009; 302:2323–2329 [View Article][PubMed]
    [Google Scholar]
  5. Zoumot Z, Wilson R. Respiratory infection in noncystic fibrosis bronchiectasis. Curr Opin Infect Dis 2010; 23:165–170 [View Article][PubMed]
    [Google Scholar]
  6. Burns JL, Gibson RL, McNamara S, Yim D, Emerson J et al. Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis 2001; 183:444–452 [View Article][PubMed]
    [Google Scholar]
  7. Moradali MF, Ghods S, Rehm BH. Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence. Front Cell Infect Microbiol 2017; 7:39 [View Article][PubMed]
    [Google Scholar]
  8. Hooper DC. New uses for new and old quinolones and the challenge of resistance. Clinical Infectious Diseases 2000; 30:243–254 [View Article]
    [Google Scholar]
  9. Andriole VT. The quinolones: past, present, and future. Clin Infect Dis 2005; 41:S113–S119 [View Article][PubMed]
    [Google Scholar]
  10. Kłodzińska SN, Priemel PA, Rades T, Mørck Nielsen H. Inhalable antimicrobials for treatment of bacterial biofilm-associated sinusitis in cystic fibrosis patients: challenges and drug delivery approaches. Int J Mol Sci 2016; 17:1688 [View Article][PubMed]
    [Google Scholar]
  11. Paulsson M, Granrot A, Ahl J, Tham J, Resman F et al. Antimicrobial combination treatment including ciprofloxacin decreased the mortality rate of Pseudomonas aeruginosa bacteraemia: a retrospective cohort study. Eur J Clin Microbiol Infect Dis 2017; 36:1187–1196 [View Article][PubMed]
    [Google Scholar]
  12. Raz R, Miron D. Oral ciprofloxacin for treatment of infection following nail puncture wounds of the foot. Clin Infect Dis 1995; 21:194–195 [View Article][PubMed]
    [Google Scholar]
  13. Mösges R, Nematian-Samani M, Eichel A. Treatment of acute otitis externa with ciprofloxacin otic 0.2% antibiotic ear solution. Ther Clin Risk Manag 2011; 7:325–336 [View Article][PubMed]
    [Google Scholar]
  14. Morrison GA, Bailey CM. Relapsing malignant otitis externa successfully treated with ciprofloxacin. J Laryngol Otol 1988; 102:872–876 [View Article][PubMed]
    [Google Scholar]
  15. Remmington T, Jahnke N, Harkensee C. Oral anti-pseudomonal antibiotics for cystic fibrosis. Cochrane Database Syst Rev 2016; 7:CD005405 [View Article][PubMed]
    [Google Scholar]
  16. Pitt TL, Sparrow M, Warner M, Stefanidou M. Survey of resistance of Pseudomonas aeruginosa from UK patients with cystic fibrosis to six commonly prescribed antimicrobial agents. Thorax 2003; 58:794–796 [View Article][PubMed]
    [Google Scholar]
  17. Landman D, Bratu S, Kochar S, Panwar M, Trehan M et al. Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, NY. J Antimicrob Chemother 2007; 60:78–82 [View Article][PubMed]
    [Google Scholar]
  18. Hooper DC. Mode of action of fluoroquinolones. Drugs 1999; 58:6–10 [View Article][PubMed]
    [Google Scholar]
  19. Levine C, Hiasa H, Marians KJ. DNA gyrase and topoisomerase IV: biochemical activities, physiological roles during chromosome replication, and drug sensitivities. Biochim Biophys Acta 1998; 1400:29–43 [View Article][PubMed]
    [Google Scholar]
  20. Wang JC. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 2002; 3:430–440 [View Article][PubMed]
    [Google Scholar]
  21. Bush NG, Evans-Roberts K, Maxwell A. DNA topoisomerases. EcoSal Plus 2015; 6: [View Article][PubMed]
    [Google Scholar]
  22. Akasaka T, Onodera Y, Tanaka M, Sato K. Cloning, expression, and enzymatic characterization of Pseudomonas aeruginosa topoisomerase IV. Antimicrob Agents Chemother 1999; 43:530–536 [View Article][PubMed]
    [Google Scholar]
  23. Kato J, Nishimura Y, Imamura R, Niki H, Hiraga S et al. New topoisomerase essential for chromosome segregation in E. coli. Cell 1990; 63:393–404[PubMed]
    [Google Scholar]
  24. Drlica K, Hiasa H, Kerns R, Malik M, Mustaev A et al. Quinolones: action and resistance updated. Curr Top Med Chem 2009; 9:981–998 [View Article][PubMed]
    [Google Scholar]
  25. Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 1997; 61:377–392[PubMed]
    [Google Scholar]
  26. Blower TR, Williamson BH, Kerns RJ, Berger JM. Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2016; 113:1706–1713 [View Article][PubMed]
    [Google Scholar]
  27. Wohlkonig A, Chan PF, Fosberry AP, Homes P, Huang J et al. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat Struct Mol Biol 2010; 17:1152–1153 [View Article][PubMed]
    [Google Scholar]
  28. Mitscher LA. Bacterial topoisomerase inhibitors: quinolone and pyridone antibacterial agents. Chem Rev 2005; 105:559–592 [View Article][PubMed]
    [Google Scholar]
  29. Jensen , Briales A, Brochmann RP, Wang H, Kragh KN et al. Formation of hydroxyl radicals contributes to the bactericidal activity of ciprofloxacin against Pseudomonas aeruginosa biofilms. Pathog Dis 2014; 70:440–443 [View Article][PubMed]
    [Google Scholar]
  30. Gade PAV, Olsen TB, Jensen , Kolpen M, Høiby N et al. Modelling of ciprofloxacin killing enhanced by hyperbaric oxygen treatment in Pseudomonas aeruginosa PAO1 biofilms. PLoS One 2018; 13:e0198909 [View Article][PubMed]
    [Google Scholar]
  31. Friedberg EC, Walker GC, Siede W. DNA Repair and Mutagenesis. ASM Press 1995
    [Google Scholar]
  32. Breidenstein EBM, Bains M, Hancock REW. Involvement of the lon protease in the SOS response triggered by ciprofloxacin in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother 2012; 56:2879–2887 [View Article][PubMed]
    [Google Scholar]
  33. Cirz RT, O'Neill BM, Hammond JA, Head SR, Romesberg FE. Defining the Pseudomonas aeruginosa SOS response and its role in the global response to the antibiotic ciprofloxacin. J Bacteriol 2006; 188:7101–7110 [View Article][PubMed]
    [Google Scholar]
  34. Courcelle J, Khodursky A, Peter B, Brown PO, Hanawalt PC. Comparative gene expression profiles following UV exposure in wild-type and SOS-deficient Escherichia coli. Genetics 2001; 158:41–64[PubMed]
    [Google Scholar]
  35. Brazas MD, Hancock REW. Ciprofloxacin induction of a susceptibility determinant in Pseudomonas aeruginosa. Antimicrob Agents Chemother 2005; 49:3222–3227 [View Article][PubMed]
    [Google Scholar]
  36. Murray JL, Kwon T, Marcotte EM, Whiteley M. Intrinsic Antimicrobial Resistance Determinants in the Superbug Pseudomonas aeruginosa. MBio 2015; 6:e0160301615 [View Article][PubMed]
    [Google Scholar]
  37. Cirz RT, Chin JK, Andes DR, de Crécy-Lagard V, Craig WA et al. Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol 2005; 3:e176 [View Article][PubMed]
    [Google Scholar]
  38. López E, Elez M, Matic I, Blázquez J. Antibiotic-mediated recombination: ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli. Mol Microbiol 2007; 64:83–93 [View Article][PubMed]
    [Google Scholar]
  39. Henderson-Begg SK, Livermore DM, Hall LM. Effect of subinhibitory concentrations of antibiotics on mutation frequency in Streptococcus pneumoniae. J Antimicrob Chemother 2006; 57:849–854 [View Article][PubMed]
    [Google Scholar]
  40. Linares JF, Gustafsson I, Baquero F, Martinez JL. Antibiotics as intermicrobial signaling agents instead of weapons. Proc Natl Acad Sci USA 2006; 103:19484–19489 [View Article][PubMed]
    [Google Scholar]
  41. de La Fuente-Núñez C, Reffuveille F, Fernández L, Hancock RE. Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies. Curr Opin Microbiol 2013; 16:580–589 [View Article][PubMed]
    [Google Scholar]
  42. Vrany JD, Stewart PS, Suci PA. Comparison of recalcitrance to ciprofloxacin and levofloxacin exhibited by Pseudomonas aeruginosa bofilms displaying rapid-transport characteristics. Antimicrob Agents Chemother 1997; 41:1352–1358 [View Article][PubMed]
    [Google Scholar]
  43. Walters MC, Roe F, Bugnicourt A, Franklin MJ, Stewart PS. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob Agents Chemother 2003; 47:317–323 [View Article][PubMed]
    [Google Scholar]
  44. Ahmed MN, Porse A, Sommer MOA, Høiby N, Ciofu O. Evolution of antibiotic resistance in biofilm and planktonic Pseudomonas aeruginosa populations exposed to subinhibitory levels of ciprofloxacin. Antimicrob Agents Chemother 2018; 62: [View Article][PubMed]
    [Google Scholar]
  45. Breidenstein EB, Khaira BK, Wiegand I, Overhage J, Hancock RE. Complex ciprofloxacin resistome revealed by screening a Pseudomonas aeruginosa mutant library for altered susceptibility. Antimicrob Agents Chemother 2008; 52:4486–4491 [View Article][PubMed]
    [Google Scholar]
  46. Zhang G, Wang C, Sui Z, Feng J. Insights into the evolutionary trajectories of fluoroquinolone resistance in Streptococcus pneumoniae. J Antimicrob Chemother 2015; 70:2499–2506 [View Article][PubMed]
    [Google Scholar]
  47. Robillard NJ, Scarpa AL. Genetic and physiological characterization of ciprofloxacin resistance in Pseudomonas aeruginosa PAO. Antimicrob Agents Chemother 1988; 32:535–539 [View Article][PubMed]
    [Google Scholar]
  48. Lee JK, Lee YS, Park YK, Kim BS. Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa. Int J Antimicrob Agents 2005; 25:290–295 [View Article][PubMed]
    [Google Scholar]
  49. Bruchmann S, Dötsch A, Nouri B, Chaberny IF, Häussler S. Quantitative contributions of target alteration and decreased drug accumulation to Pseudomonas aeruginosa fluoroquinolone resistance. Antimicrob Agents Chemother 2013; 57:1361–1368 [View Article][PubMed]
    [Google Scholar]
  50. Wydmuch Z, Skowronek-Ciołek O, Cholewa K, Mazurek U, Pacha J et al. GyrA mutations in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa in a Silesian Hospital in Poland. Pol J Microbiol 2005; 54:201–206[PubMed]
    [Google Scholar]
  51. Pasca MR, Dalla Valle C, de Jesus Lopes Ribeiro AL, Buroni S, Papaleo MC et al. Evaluation of fluoroquinolone resistance mechanisms in Pseudomonas aeruginosa multidrug resistance clinical isolates. Microb Drug Resist 2012; 18:23–32 [View Article][PubMed]
    [Google Scholar]
  52. Higgins PG, Fluit AC, Milatovic D, Verhoef J, Schmitz FJ. Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa. Int J Antimicrob Agents 2003; 21:409–413 [View Article][PubMed]
    [Google Scholar]
  53. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry 2014; 53:1565–1574 [View Article][PubMed]
    [Google Scholar]
  54. Aldred KJ, McPherson SA, Turnbough CL, Kerns RJ, Osheroff N. Topoisomerase IV-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance. Nucleic Acids Res 2013; 41:4628–4639 [View Article][PubMed]
    [Google Scholar]
  55. Willmott CJ, Maxwell A. A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex. Antimicrob Agents Chemother 1993; 37:126–127 [View Article][PubMed]
    [Google Scholar]
  56. Barnard FM, Maxwell A. Interaction between DNA gyrase and quinolones: effects of alanine mutations at GyrA subunit residues Ser(83) and Asp(87). Antimicrob Agents Chemother 2001; 45:1994–2000 [View Article][PubMed]
    [Google Scholar]
  57. Aldred KJ, McPherson SA, Wang P, Kerns RJ, Graves DE et al. Drug interactions with Bacillus anthracis topoisomerase IV: biochemical basis for quinolone action and resistance. Biochemistry 2012; 51:370–381 [View Article][PubMed]
    [Google Scholar]
  58. Wong A, Kassen R. Parallel evolution and local differentiation in quinolone resistance in Pseudomonas aeruginosa. Microbiology 2011; 157:937–944 [View Article][PubMed]
    [Google Scholar]
  59. Poole K. Pseudomonas aeruginosa: resistance to the max. Front Microbiol 2011; 2:65 [View Article][PubMed]
    [Google Scholar]
  60. Zgurskaya HI. Multicomponent drug efflux complexes: architecture and mechanism of assembly. Future Microbiol 2009; 4:919–932 [View Article][PubMed]
    [Google Scholar]
  61. Nikaido H. Multiple antibiotic resistance and efflux. Curr Opin Microbiol 1998; 1:516–523 [View Article][PubMed]
    [Google Scholar]
  62. Poole K. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 2005; 56:20–51 [View Article][PubMed]
    [Google Scholar]
  63. Oh H, Stenhoff J, Jalal S, Wretlind B. Role of efflux pumps and mutations in genes for topoisomerases II and IV in fluoroquinolone-resistant Pseudomonas aeruginosa strains. Microb Drug Resist 2003; 9:323–328 [View Article][PubMed]
    [Google Scholar]
  64. Goli HR, Nahaei MR, Rezaee MA, Hasani A, Samadi Kafil H et al. Contribution of mexAB-oprM and mexXY (-oprA) efflux operons in antibiotic resistance of clinical Pseudomonas aeruginosa isolates in Tabriz, Iran. Infect Genet Evol 2016; 45:75–82 [View Article][PubMed]
    [Google Scholar]
  65. Llanes C, Köhler T, Patry I, Dehecq B, van Delden C et al. Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin. Antimicrob Agents Chemother 2011; 55:5676–5684 [View Article][PubMed]
    [Google Scholar]
  66. Morita Y, Tomida J, Kawamura Y. Efflux-mediated fluoroquinolone resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7: identification of a novel MexS variant involved in upregulation of the mexEF-oprN multidrug efflux operon. Front Microbiol 2015; 6:8 [View Article][PubMed]
    [Google Scholar]
  67. Tai AS, Bell SC, Kidd TJ, Trembizki E, Buckley C et al. Genotypic diversity within a single Pseudomonas aeruginosa strain commonly shared by australian patients with cystic fibrosis. PLoS One 2015; 10:e0144022 [View Article][PubMed]
    [Google Scholar]
  68. Sun J, Deng Z, Yan A. Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun 2014; 453:254–267 [View Article][PubMed]
    [Google Scholar]
  69. Jørgensen KM, Wassermann T, Jensen , Hengzuang W, Molin S et al. Sublethal ciprofloxacin treatment leads to rapid development of high-level ciprofloxacin resistance during long-term experimental evolution of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2013; 57:4215–4221 [View Article][PubMed]
    [Google Scholar]
  70. Henrichfreise B, Wiegand I, Pfister W, Wiedemann B. Resistance mechanisms of multiresistant Pseudomonas aeruginosa strains from Germany and correlation with hypermutation. Antimicrob Agents Chemother 2007; 51:4062–4070 [View Article][PubMed]
    [Google Scholar]
  71. Jalal S, Ciofu O, Hoiby N, Gotoh N, Wretlind B. Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother 2000; 44:710–712 [View Article][PubMed]
    [Google Scholar]
  72. Jalal S, Wretlind B. Mechanisms of quinolone resistance in clinical strains of Pseudomonas aeruginosa. Microb Drug Resist 1998; 4:257–261 [View Article][PubMed]
    [Google Scholar]
  73. Kiser TH, Obritsch MD, Jung R, MacLaren R, Fish DN. Efflux pump contribution to multidrug resistance in clinical isolates of Pseudomonas aeruginosa. Pharmacotherapy 2010; 30:632–638 [View Article][PubMed]
    [Google Scholar]
  74. Purssell A, Poole K. Functional characterization of the NfxB repressor of the mexCD-oprJ multidrug efflux operon of Pseudomonas aeruginosa. Microbiology 2013; 159:2058–2073 [View Article][PubMed]
    [Google Scholar]
  75. Monti MR, Morero NR, Miguel V, Argaraña CE. nfxB as a novel target for analysis of mutation spectra in Pseudomonas aeruginosa. PLoS One 2013; 8:e66236 [View Article][PubMed]
    [Google Scholar]
  76. Richardot C, Juarez P, Jeannot K, Patry I, Plésiat P et al. Amino acid substitutions account for most MexS alterations in clinical nfxC mutants of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2016; 60:2302–2310 [View Article][PubMed]
    [Google Scholar]
  77. Hocquet D, Muller A, Blanc K, Plésiat P, Talon D et al. Relationship between antibiotic use and incidence of MexXY-OprM overproducers among clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2008; 52:1173–1175 [View Article][PubMed]
    [Google Scholar]
  78. Smith EE, Buckley DG, Wu Z, Saenphimmachak C, Hoffman LR et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci USA 2006; 103:8487–8492 [View Article][PubMed]
    [Google Scholar]
  79. Aires JR, Köhler T, Nikaido H, Plésiat P. Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother 1999; 43:2624–2628 [View Article][PubMed]
    [Google Scholar]
  80. Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev 2009; 22:582–610 [View Article][PubMed]
    [Google Scholar]
  81. Réjiba S, Aubry A, Petitfrère S, Jarlier V, Cambau E. Contribution of ParE mutation and efflux to ciprofloxacin resistance in Pseudomonas aeruginosa clinical isolates. J Chemother 2008; 20:749–752 [View Article][PubMed]
    [Google Scholar]
  82. Alekshun MN, Levy SB. Molecular mechanisms of antibacterial multidrug resistance. Cell 2007; 128:1037–1050 [View Article][PubMed]
    [Google Scholar]
  83. Wei Q, Tarighi S, Dötsch A, Häussler S, Müsken M et al. Phenotypic and genome-wide analysis of an antibiotic-resistant small colony variant (SCV) of Pseudomonas aeruginosa. PLoS One 2011; 6:e29276 [View Article][PubMed]
    [Google Scholar]
  84. Lucchetti-Miganeh C, Redelberger D, Chambonnier G, Rechenmann F, Elsen S et al. Pseudomonas aeruginosa genome evolution in patients and under the Hospital Environment. Pathogens 2014; 3:309–340 [View Article][PubMed]
    [Google Scholar]
  85. Lomholt JA, Kilian M. Ciprofloxacin susceptibility of Pseudomonas aeruginosa isolates from keratitis. Br J Ophthalmol 2003; 87:1238–1240 [View Article][PubMed]
    [Google Scholar]
  86. Le Thomas I, Couetdic G, Clermont O, Brahimi N, Plésiat P et al. In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by ciprofloxacin therapy. J Antimicrob Chemother 2001; 48:553–555 [View Article][PubMed]
    [Google Scholar]
  87. Wang Y-T, Lee M-F, Peng C-F. Mutations in the quinolone resistance-determining regions associated with ciprofloxacin resistance in Pseudomonas aeruginosa isolates from Southern Taiwan. Biomarkers and Genomic Medicine 2014; 6:79–83 [View Article]
    [Google Scholar]
  88. Cho HH, Kwon KC, Kim S, Koo SH. Correlation between virulence genotype and fluoroquinolone resistance in carbapenem-resistant Pseudomonas aeruginosa. Ann Lab Med 2014; 34:286–292 [View Article][PubMed]
    [Google Scholar]
  89. Mouneimné H, Robert J, Jarlier V, Cambau E. Type II topoisomerase mutations in ciprofloxacin-resistant strains of Pseudomonas aeruginosa. Antimicrob Agents Chemother 1999; 43:62–66 [View Article][PubMed]
    [Google Scholar]
  90. Nouri R, Ahangarzadeh Rezaee M, Hasani A, Aghazadeh M, Asgharzadeh M. The role of gyrA and parC mutations in fluoroquinolones-resistant Pseudomonas aeruginosa isolates from Iran. Braz J Microbiol 2016; 47:925–930 [View Article][PubMed]
    [Google Scholar]
  91. Dunham SA, McPherson CJ, Miller AA. The relative contribution of efflux and target gene mutations to fluoroquinolone resistance in recent clinical isolates of Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis 2010; 29:279–288 [View Article][PubMed]
    [Google Scholar]
  92. Feng Y, Jonker MJ, Moustakas I, Brul S, Ter Kuile BH. Dynamics of mutations during development of resistance by Pseudomonas aeruginosa against five antibiotics. Antimicrob Agents Chemother 2016; 60:4229–4236 [View Article][PubMed]
    [Google Scholar]
  93. Jacoby GA. Mechanisms of resistance to quinolones. Clin Infect Dis 2005; 41:S120–S126 [View Article][PubMed]
    [Google Scholar]
  94. Marvig RL, Sommer LM, Molin S, Johansen HK. Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis. Nat Genet 2015; 47:57–64 [View Article][PubMed]
    [Google Scholar]
  95. Su HC, Ramkissoon K, Doolittle J, Clark M, Khatun J et al. The development of ciprofloxacin resistance in Pseudomonas aeruginosa involves multiple response stages and multiple proteins. Antimicrob Agents Chemother 2010; 54:4626–4635 [View Article][PubMed]
    [Google Scholar]
  96. Peng J, Cao J, Ng FM, Hill J. Pseudomonas aeruginosa develops Ciprofloxacin resistance from low to high level with distinctive proteome changes. J Proteomics 2017; 152:75–87 [View Article][PubMed]
    [Google Scholar]
  97. Correia S, Poeta P, Hébraud M, Capelo JL, Igrejas G. Mechanisms of quinolone action and resistance: where do we stand?. J Med Microbiol 2017; 66:551–559 [View Article][PubMed]
    [Google Scholar]
  98. Chávez-Jacobo VM, Hernández-Ramírez KC, Romo-Rodríguez P, Pérez-Gallardo RV, Campos-García J et al. CrpP Is a Novel Ciprofloxacin-Modifying Enzyme Encoded by the Pseudomonas aeruginosa pUM505 Plasmid. Antimicrob Agents Chemother 2018; 62:e02629-17 [View Article][PubMed]
    [Google Scholar]
  99. Ogbolu DO, Daini OA, Ogunledun A, Alli AO, Webber MA. High levels of multidrug resistance in clinical isolates of Gram-negative pathogens from Nigeria. Int J Antimicrob Agents 2011; 37:62–66 [View Article][PubMed]
    [Google Scholar]
  100. Liu J, Yang L, Chen D, Peters BM, Li L et al. Complete sequence of pBM413, a novel multidrug resistance megaplasmid carrying qnrVC6 and blaIMP-45 from Pseudomonas aeruginosafrom pseudomonas aeruginosa. Int J Antimicrob Agents 2018; 51:145–150 [View Article][PubMed]
    [Google Scholar]
  101. Wang F, Wu K, Sun J, Wang Q, Chen Q et al. Novel ISCR1-linked resistance genes found in multidrug-resistant Gram-negative bacteria in southern China. Int J Antimicrob Agents 2012; 40:404–408 [View Article][PubMed]
    [Google Scholar]
  102. World Health Organization Antimicrobial resistance: Global report on surveillance; 2014 http://www.who.int/drugresistance/documents/surveillancereport/en/
  103. Cipolla D, Blanchard J, Gonda I. Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics 2016; 8:6 [View Article][PubMed]
    [Google Scholar]
  104. Ermertcan S, Hoşgör M, Tünger O, Coşar G. Investigation of synergism of meropenem and ciprofloxacin against Pseudomonas aeruginosa and Acinetobacter strains isolated from intensive care unit infections. Scand J Infect Dis 2001; 33:818–821[PubMed]
    [Google Scholar]
  105. Rhee MK, Kowalski RP, Romanowski EG, Mah FS, Ritterband DC et al. A laboratory evaluation of antibiotic therapy for ciprofloxacin-resistant Pseudomonas aeruginosa. Am J Ophthalmol 2004; 138:226–230 [View Article][PubMed]
    [Google Scholar]
  106. Lister PD, Wolter DJ, Wickman PA, Reisbig MD. Levofloxacin/imipenem prevents the emergence of high-level resistance among Pseudomonas aeruginosa strains already lacking susceptibility to one or both drugs. J Antimicrob Chemother 2006; 57:999–1003 [View Article][PubMed]
    [Google Scholar]
  107. Michéa-Hamzehpour M, Pechère JC, Marchou B, Auckenthaler R. Combination therapy: a way to limit emergence of resistance?. Am J Med 1986; 80:138–142 [View Article][PubMed]
    [Google Scholar]
  108. Pankuch GA, Lin G, Seifert H, Appelbaum PC. Activity of meropenem with and without ciprofloxacin and colistin against Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrob Agents Chemother 2008; 52:333–336 [View Article][PubMed]
    [Google Scholar]
  109. Andersson DI, Hughes D. Antibiotic resistance and its cost: is it possible to reverse resistance?. Nat Rev Microbiol 2010; 8:260–271 [View Article][PubMed]
    [Google Scholar]
  110. Gottesman BS, Carmeli Y, Shitrit P, Chowers M. Impact of quinolone restriction on resistance patterns of Escherichia coli isolated from urine by culture in a community setting. Clin Infect Dis 2009; 49:869–875 [View Article][PubMed]
    [Google Scholar]
  111. Johnsen PJ, Townsend JP, Bøhn T, Simonsen GS, Sundsfjord A et al. Factors affecting the reversal of antimicrobial-drug resistance. Lancet Infect Dis 2009; 9:357–364 [View Article][PubMed]
    [Google Scholar]
  112. Imamovic L, Sommer MO. Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development. Sci Transl Med 2013; 5:204ra132 [View Article][PubMed]
    [Google Scholar]
  113. Pál C, Papp B, Lázár V. Collateral sensitivity of antibiotic-resistant microbes. Trends Microbiol 2015; 23:401–407 [View Article][PubMed]
    [Google Scholar]
  114. Lázár V, Pal Singh G, Spohn R, Nagy I, Horváth B et al. Bacterial evolution of antibiotic hypersensitivity. Mol Syst Biol 2013; 9:700 [View Article][PubMed]
    [Google Scholar]
  115. Masuda N, Sakagawa E, Ohya S, Gotoh N, Nishino T. Hypersusceptibility of the Pseudomonas aeruginosa nfxB mutant to beta-lactams due to reduced expression of the ampC beta-lactamase. Antimicrob Agents Chemother 2001; 45:1284–1286 [View Article][PubMed]
    [Google Scholar]
  116. Vettoretti L, Plésiat P, Muller C, El Garch F, Phan G et al. Efflux unbalance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother 2009; 53:1987–1997 [View Article][PubMed]
    [Google Scholar]
  117. Fernández L, Hancock RE. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev 2012; 25:661–681 [View Article][PubMed]
    [Google Scholar]
  118. Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare?. Clin Infect Dis 2002; 34:634–640 [View Article][PubMed]
    [Google Scholar]
  119. Wolter DJ, Schmidtke AJ, Hanson ND, Lister PD. Increased expression of ampC in Pseudomonas aeruginosa mutants selected with ciprofloxacin. Antimicrob Agents Chemother 2007; 51:2997–3000 [View Article][PubMed]
    [Google Scholar]
  120. Poole K, Gotoh N, Tsujimoto H, Zhao Q, Wada A et al. Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol Microbiol 1996; 21:713–725 [View Article][PubMed]
    [Google Scholar]
  121. Köhler T, Michéa-Hamzehpour M, Henze U, Gotoh N, Curty LK et al. Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol Microbiol 1997; 23:345–354 [View Article][PubMed]
    [Google Scholar]
  122. Tanimoto K, Tomita H, Fujimoto S, Okuzumi K, Ike Y. Fluoroquinolone enhances the mutation frequency for meropenem-selected carbapenem resistance in Pseudomonas aeruginosa, but use of the high-potency drug doripenem inhibits mutant formation. Antimicrob Agents Chemother 2008; 52:3795–3800 [View Article][PubMed]
    [Google Scholar]
  123. Lee RS, Behr MA. The implications of whole-genome sequencing in the control of tuberculosis. Ther Adv Infect Dis 2016; 3:47–62 [View Article][PubMed]
    [Google Scholar]
  124. Köser CU, Ellington MJ, Peacock SJ. Whole-genome sequencing to control antimicrobial resistance. Trends Genet 2014; 30:401–407 [View Article][PubMed]
    [Google Scholar]
  125. Kwong JC, McCallum N, Sintchenko V, Howden BP. Whole genome sequencing in clinical and public health microbiology. Pathology 2015; 47:199–210 [View Article][PubMed]
    [Google Scholar]
  126. Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 2015; 10:845–858 [View Article][PubMed]
    [Google Scholar]
  127. Yang X, Xing B, Liang C, Ye Z, Zhang Y. Prevalence and fluoroquinolone resistance of pseudomonas aeruginosa in a hospital of South China. Int J Clin Exp Med 2015; 8:1386–1390[PubMed]
    [Google Scholar]
  128. Akasaka T, Tanaka M, Yamaguchi A, Sato K. Type II topoisomerase mutations in fluoroquinolone-resistant clinical strains of Pseudomonas aeruginosa isolated in 1998 and 1999: role of target enzyme in mechanism of fluoroquinolone resistance. Antimicrob Agents Chemother 2001; 45:2263–2268 [View Article][PubMed]
    [Google Scholar]
  129. Wong A, Rodrigue N, Kassen R. Genomics of adaptation during experimental evolution of the opportunistic pathogen Pseudomonas aeruginosa. PLoS Genet 2012; 8:e1002928 [View Article][PubMed]
    [Google Scholar]
  130. Cabot G, Zamorano L, Moyà B, Juan C, Navas A et al. Evolution of Pseudomonas aeruginosa antimicrobial resistance and fitness under low and high mutation rates. Antimicrob Agents Chemother 2016; 60:1767–1778 [View Article][PubMed]
    [Google Scholar]
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