Advertisement

Antibiotic Tolerance and Resistance in Biofilms

  • Oana Ciofu
  • Tim Tolker-Nielsen
Chapter

Abstract

One of the most important features of microbial biofilms is their tolerance to antimicrobial agents and components of the host immune system. The difficulty of treating biofilm infections with antibiotics is a major clinical problem. Although antibiotics may decrease the number of bacteria in biofilms, they will not completely eradicate the bacteria in vivo which may have important clinical consequences in form of relapses of the infection.

Keywords

Efflux Pump Planktonic Cell Persister Cell Antibiotic Tolerance Chronic Lung Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Alipour M, Suntres ZE, Omri A (2009) Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa. J Antimicrob Chemother 64:317–325CrossRefPubMedGoogle Scholar
  2. Bagge N, Ciofu O, Skovgaard LT, Hoiby N (2000) Rapid development in vitro and in vivo of resistance to ceftazidime in biofilm-growing Pseudomonas aeruginosa due to chromosomal beta-lactamase. Apmis 108:589–600CrossRefPubMedGoogle Scholar
  3. Bagge N, Hentzer M, Andersen JB, Ciofu O, Givskov M, Hoiby N (2004a) Dynamics and spatial distribution of beta-lactamase expression in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 48:1168–1174CrossRefPubMedGoogle Scholar
  4. Bagge N, Schuster M, Hentzer M, Ciofu O, Givskov M, Greenberg EP et al (2004b) Pseudomonas aeruginosa biofilms exposed to imipenem exhibit changes in global gene expression and beta-lactamase and alginate production. Antimicrob Agents Chemother 48:1175–1187CrossRefPubMedGoogle Scholar
  5. Barraud N, Hassett DJ, Hwang SH, Rice SA, Kjelleberg S, Webb JS (2006) Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa. J Bacteriol 188:7344–7353CrossRefPubMedGoogle Scholar
  6. Bjarnsholt T, Jensen PO, Burmolle M, Hentzer M, Haagensen JA, Hougen HP et al (2005) Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151:373–383CrossRefPubMedGoogle Scholar
  7. Bjarnsholt T, Jensen PO, Fiandaca MJ, Pedersen J, Hansen CR, Andersen CB et al (2009) Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr Pulmonol 44:547–558CrossRefPubMedGoogle Scholar
  8. Boles BR, Singh PK (2008) Endogenous oxidative stress produces diversity and adaptability in biofilm communities. Proc Natl Acad Sci USA 105:12503–12508CrossRefPubMedGoogle Scholar
  9. Brooun A, Liu S, Lewis K (2000) A dose-response study of antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 44:640–646CrossRefPubMedGoogle Scholar
  10. Ciofu O (2003) Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response. APMIS Suppl 1–47Google Scholar
  11. Ciofu O, Bagge N, Hoiby N (2002) Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection. Apmis 110:881–891CrossRefPubMedGoogle Scholar
  12. Ciofu O, Beveridge TJ, Kadurugamuwa J, Walther-Rasmussen J, Hoiby N (2000) Chromosomal beta-lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa. J Antimicrob Chemother 45:9–13CrossRefPubMedGoogle Scholar
  13. Ciofu O, Giwercman B, Pedersen SS, Hoiby N (1994) Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center. Apmis 102:674–680CrossRefPubMedGoogle Scholar
  14. Ciofu O, Høiby N (2007) Cystic Fibrosis-coping with resistance. In: Gould, van der Meer (eds) Antibiotic policies: fighting resistance. Springer, New York, pp 149–174Google Scholar
  15. Ciofu O, Petersen TD, Jensen P, Hoiby N (1999) Avidity of anti-P aeruginosa antibodies during chronic infection in patients with cystic fibrosis. Thorax 54:141–144CrossRefPubMedGoogle Scholar
  16. Ciofu O, Riis B, Pressler T, Poulsen HE, Hoiby N (2005) Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation. Antimicrob Agents Chemother 49:2276–2282CrossRefPubMedGoogle Scholar
  17. Conibear TC, Collins SL, Webb JS (2009) Role of mutation in Pseudomonas aeruginosa biofilm development. PLoS One 4:e6289CrossRefPubMedGoogle Scholar
  18. De Kievit TR, Parkins MD, Gillis RJ, Srikumar R, Ceri H, Poole K et al (2001) Multidrug efflux pumps: expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 45:1761–1770CrossRefPubMedGoogle Scholar
  19. De Groote VN, Verstraeten N, Fauvart M, Kint CI, Verbeeck AM, Beullens S et al (2009) Novel persistence genes in Pseudomonas aeruginosa identified by high-throughput screening. FEMS Microbiol Lett 297:73–77Google Scholar
  20. Doring G, Conway SP, Heijerman HG, Hodson ME, Hoiby N, Smyth A et al (2000) Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 16:749–767CrossRefPubMedGoogle Scholar
  21. Doring G, Hoiby N (2004) Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. J Cyst Fibros 3:67–91CrossRefPubMedGoogle Scholar
  22. Drenkard E, Ausubel FM (2002) Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416:740–743CrossRefPubMedGoogle Scholar
  23. Driffield K, Miller K, Bostock JM, O’Neill AJ, Chopra I (2008) Increased mutability of Pseudomonas aeruginosa in biofilms. J Antimicrob Chemother 61:1053–1056CrossRefPubMedGoogle Scholar
  24. Ferroni A, Guillemot D, Moumile K, Bernede C, Le BM, Waernessyckle S et al (2009) Effect of mutator P. aeruginosa on antibiotic resistance acquisition and respiratory function in cystic fibrosis. Pediatr Pulmonol 44:820–825CrossRefPubMedGoogle Scholar
  25. Gillis RJ, White KG, Choi KH, Wagner VE, Schweizer HP, Iglewski BH (2005) Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 49:3858–3867CrossRefPubMedGoogle Scholar
  26. Giwercman B, Jensen ET, Hoiby N, Kharazmi A, Costerton JW (1991) Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. Antimicrob Agents Chemother 35:1008–1010PubMedGoogle Scholar
  27. Giwercman B, Lambert PA, Rosdahl VT, Shand GH, Hoiby N (1990) Rapid emergence of resistance in Pseudomonas aeruginosa in cystic fibrosis patients due to in-vivo selection of stable partially derepressed beta-lactamase producing strains. J Antimicrob Chemother 26:247–259CrossRefPubMedGoogle Scholar
  28. Hansen CR, Pressler T, Hoiby N (2008) Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience. J Cyst Fibros 7:523–530CrossRefPubMedGoogle Scholar
  29. Hassett DJ, Ma JF, Elkins JG, McDermott TR, Ochsner UA, West SE et al (1999) Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. Mol Microbiol 34:1082–1093CrossRefPubMedGoogle Scholar
  30. Hentzer M, Eberl L, Givskov M (2005) Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms 2:37–61CrossRefGoogle Scholar
  31. Hill D, Rose B, Pajkos A, Robinson M, Bye P, Bell S et al (2005) Antibiotic susceptabilities of Pseudomonas aeruginosa isolates derived from patients with cystic fibrosis under aerobic, anaerobic, and biofilm conditions. J Clin Microbiol 43:5085–5090CrossRefPubMedGoogle Scholar
  32. Hoboth C, Hoffmann R, Eichner A, Henke C, Schmoldt S, Imhof A et al (2009) Dynamics of adaptive microevolution of hypermutable Pseudomonas aeruginosa during chronic pulmonary infection in patients with cystic fibrosis. J Infect Dis 200:118–130CrossRefPubMedGoogle Scholar
  33. Hoffman LR, D’Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI (2005) Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436:1171–1175CrossRefPubMedGoogle Scholar
  34. Hoiby N (2001) Inflammation and infection in cystic fibrosis – hen or egg? Eur Respir J 17:4–5CrossRefPubMedGoogle Scholar
  35. Islam S, Oh H, Jalal S, Karpati F, Ciofu O, Hoiby N et al (2009) Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Clin Microbiol Infect 15:60–66CrossRefPubMedGoogle Scholar
  36. Jalal S, Ciofu O, Hoiby N, Gotoh N, Wretlind B (2000) Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother 44:710–712CrossRefPubMedGoogle Scholar
  37. Johansen HK, Moskowitz SM, Ciofu O, Pressler T, Hoiby N (2008) Spread of colistin resistant non-mucoid Pseudomonas aeruginosa among chronically infected Danish cystic fibrosis patients. J Cyst Fibros 7:391–397CrossRefPubMedGoogle Scholar
  38. Keays T, Ferris W, Vandemheen KL, Chan F, Yeung SW, Mah TF et al (2009) A retrospective analysis of biofilm antibiotic susceptibility testing: a better predictor of clinical response in cystic fibrosis exacerbations. J Cyst Fibros 8:122–127CrossRefPubMedGoogle Scholar
  39. Kim J, Hahn JS, Franklin MJ, Stewart PS, Yoon J (2009) Tolerance of dormant and active cells in Pseudomonas aeruginosa PA01 biofilm to antimicrobial agents. J Antimicrob Chemother 63:129–135CrossRefPubMedGoogle Scholar
  40. Kvist M, Hancock V, Klemm P (2008) Inactivation of efflux pumps abolishes bacterial biofilm formation. Appl Environ Microbiol 74:7376–7382CrossRefPubMedGoogle Scholar
  41. Lechtzin N, John M, Irizarry R, Merlo C, Diette GB, Boyle MP (2006) Outcomes of adults with cystic fibrosis infected with antibiotic-resistant Pseudomonas aeruginosa. Respiration 73:27–33CrossRefPubMedGoogle Scholar
  42. Lewis K (2000) Programmed death in bacteria. Microbiol Mol Biol Rev 64:503–514CrossRefPubMedGoogle Scholar
  43. Li XZ, Ma D, Livermore DM, Nikaido H (1994) Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to beta-lactam resistance. Antimicrob Agents Chemother 38:1742–1752PubMedGoogle Scholar
  44. Macia MD, Blanquer D, Togores B, Sauleda J, Perez JL, Oliver A (2005) Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa strains causing chronic lung infections. Antimicrob Agents Chemother 49:3382–3386CrossRefPubMedGoogle Scholar
  45. Macia MD, Borrell N, Segura M, Gomez C, Perez JL, Oliver A (2006) Efficacy and potential for resistance selection of antipseudomonal treatments in a mouse model of lung infection by hypermutable Pseudomonas aeruginosa. Antimicrob Agents Chemother 50:975–983CrossRefPubMedGoogle Scholar
  46. Mah TF, Pitts B, Pellock B, Walker GC, Stewart PS, O’Toole GA (2003) A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426:306–310CrossRefPubMedGoogle Scholar
  47. Mai-Prochnow A, Lucas-Elio P, Egan S, Thomas T, Webb JS, Sanchez-Amat A. et al (2008) Hydrogen peroxide linked to lysine oxidase activity facilitates biofilm differentiation and dispersal in several gram-negative bacteria. J Bacteriol 190:5493–5501CrossRefPubMedGoogle Scholar
  48. Mandsberg LF, Ciofu O, Kirkby N, Christiansen LE, Poulsen HE, Hoiby N (2009) Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system. Antimicrob Agents Chemother 53:2483–2491CrossRefPubMedGoogle Scholar
  49. McPhee JB, Lewenza S, Hancock RE (2003) Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol Microbiol 50:205–217CrossRefPubMedGoogle Scholar
  50. Moskowitz SM, Foster JM, Emerson J, Burns JL (2004) Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol 42:1915–1922CrossRefPubMedGoogle Scholar
  51. Mulet X, Macia MD, Mena A, Juan C, Perez JL, Oliver A (2009) Azithromycin in Pseudomonas aeruginosa biofilms: bactericidal activity and selection of nfxB mutants. Antimicrob Agents Chemother 53:1552–1560CrossRefPubMedGoogle Scholar
  52. Murakami K, Ono T, Viducic D, Kayama S, Mori M, Hirota K. et al (2005) Role for rpoS gene of Pseudomonas aeruginosa in antibiotic tolerance. FEMS Microbiol Lett 242:161–167CrossRefPubMedGoogle Scholar
  53. Nichols WW, Evans MJ, Slack MP, Walmsley HL (1989) The penetration of antibiotics into aggregates of mucoid and non-mucoid Pseudomonas aeruginosa. J Gen Microbiol 135:1291–1303PubMedGoogle Scholar
  54. Oliver A, Canton R, Campo P, Baquero F, Blazquez J (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–1254CrossRefPubMedGoogle Scholar
  55. Oliver A, Levin BR, Juan C, Baquero F, Blazquez J (2004) Hypermutation and the preexistence of antibiotic-resistant Pseudomonas aeruginosa mutants: implications for susceptibility testing and treatment of chronic infections. Antimicrob Agents Chemother 48:4226–4233CrossRefPubMedGoogle Scholar
  56. Oliver A, Sanchez JM, Blazquez J (2002) Characterization of the GO system of Pseudomonas aeruginosa. FEMS Microbiol Lett 217:31–35CrossRefPubMedGoogle Scholar
  57. Pamp SJ, Gjermansen M, Johansen HK, Tolker-Nielsen T (2008) Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes. Mol Microbiol 68:223–240CrossRefPubMedGoogle Scholar
  58. Park S, You X, Imlay JA (2005) Substantial DNA damage from submicromolar intracellular hydrogen peroxide detected in Hpx-mutants of Escherichia coli. Proc Natl Acad Sci USA 102:9317–9322CrossRefPubMedGoogle Scholar
  59. Poole K (2008) Bacterial multidrug efflux pumps serve other functions. Microbe 3:179–185. Ref type: genericGoogle Scholar
  60. Shih PC, Huang CT (2002) Effects of quorum-sensing deficiency on Pseudomonas aeruginosa biofilm formation and antibiotic resistance. J Antimicrob Chemother 49:309–314CrossRefPubMedGoogle Scholar
  61. Spoering AL, Lewis K (2001) Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J Bacteriol 183:6746–6751CrossRefPubMedGoogle Scholar
  62. Takahashi A, Yomoda S, Ushijima Y, Kobayashi I, Inoue M (1995) Ofloxacin, norfloxacin and ceftazidime increase the production of alginate and promote the formation of biofilm of Pseudomonas aeruginosa in vitro. J Antimicrob Chemother 36:743–745CrossRefPubMedGoogle Scholar
  63. Trent MS, Ribeiro AA, Lin S, Cotter RJ, Raetz CR (2001) An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor. J Biol Chem 276:43122–43131CrossRefPubMedGoogle Scholar
  64. Vazquez-Laslop N, Lee H, Neyfakh AA (2006) Increased persistence in Escherichia coli caused by controlled expression of toxins or other unrelated proteins. J Bacteriol 188:3494–3497CrossRefPubMedGoogle Scholar
  65. Viducic D, Ono T, Murakami K, Susilowati H, Kayama S, Hirota K et al (2006) Functional analysis of spoT, relA and dksA genes on quinolone tolerance in Pseudomonas aeruginosa under nongrowing condition. Microbiol Immunol 50:349–357PubMedGoogle Scholar
  66. Walters MC, III, Roe F, Bugnicourt A, Franklin MJ, Stewart PS (2003) Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob Agents Chemother 47:317–323CrossRefPubMedGoogle Scholar
  67. Werner E, Roe F, Bugnicourt A, Franklin MJ, Heydorn A, Molin S et al (2004) Stratified growth in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 70:6188–6196CrossRefPubMedGoogle Scholar
  68. Zhang L, Mah TF (2008) Involvement of a novel efflux system in biofilm-specific resistance to antibiotics. J Bacteriol 190:4447–4452CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Faculty of Health Sciences, Department of International Health,Immunology and Microbiology, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of International Health, Immunology and Microbiology, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark

Personalised recommendations