Skip to main content

Advertisement

SpringerLink
Log in

Biofilm-specific antibiotic tolerance and resistance

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Biofilms are heterogeneous structures composed of bacterial cells surrounded by a matrix and attached to solid surfaces. The bacteria here are 100 to 1,000 times more tolerant to antimicrobials than corresponding planktonic cells. Biofilms can be difficult to eradicate when they cause biofilm-related diseases, e.g., implant infections, cystic fibrosis, urinary tract infections, and periodontal diseases. A number of phenotypic features of the biofilm can be involved in biofilm-specific tolerance and resistance. Little is known about the molecular mechanisms involved. The current review deals with both phenotypic and molecular mechanisms of biofilm-specific antibiotic tolerance and resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Flemming HC, Wingender J (2010) The biofilm matrix. Nat Rev Microbiol 8(9):623–633

    CAS  PubMed  Google Scholar 

  2. Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A (1999) The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol 37(6):1771–1776

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Walters MC 3rd, 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(1):317–323

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Chiang WC, Nilsson M, Jensen PØ, Høiby N, Nielsen TE, Givskov M, Tolker-Nielsen T (2013) Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 57(5):2352–2361. doi:10.1128/AAC.00001-13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Lazăr V, Chifiriuc MC (2010) Medical significance and new therapeutical strategies for biofilm associated infections. Roum Arch Microbiol Immunol 69(3):125–138

    PubMed  Google Scholar 

  6. de Beer D, Stoodley P, Lewandowski Z (1997) Measurement of local diffusion coefficients in biofilms by microinjection and confocal microscopy. Biotechnol Bioeng 53(2):151–158

    Article  PubMed  Google Scholar 

  7. Fux CA, Wilson S, Stoodley P (2004) Detachment characteristics and oxacillin resistance of Staphyloccocus aureus biofilm emboli in an in vitro catheter infection model. J Bacteriol 186(14):4486–4491

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Hall-Stoodley L, Stoodley P (2009) Evolving concepts in biofilm infections. Cell Microbiol 11(7):1034–1043. doi:10.1111/j.1462-5822.2009.01323.x

    Article  CAS  PubMed  Google Scholar 

  9. Ciofu O, Tolker-Nielsen T, Jensen PØ, Wang H, Høiby N (2014) Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients. Adv Drug Deliv Rev. doi:10.1016/j.addr.2014.11.017

    PubMed  Google Scholar 

  10. Werner E, Roe F, Bugnicourt A, Franklin MJ, Heydorn A, Molin S, Pitts B, Stewart PS (2004) Stratified growth in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 70(10):6188–6196

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. 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(1):223–240. doi:10.1111/j.1365-2958.2008.06152.x

    Article  CAS  PubMed  Google Scholar 

  12. Brown MR, Allison DG, Gilbert P (1988) Resistance of bacterial biofilms to antibiotics: a growth-rate related effect? J Antimicrob Chemother 22(6):777–780

    Article  CAS  PubMed  Google Scholar 

  13. Xu KD, McFeters GA, Stewart PS (2000) Biofilm resistance to antimicrobial agents. Microbiology 146(Pt 3):547–549

    CAS  PubMed  Google Scholar 

  14. Bernier SP, Lebeaux D, DeFrancesco AS, Valomon A, Soubigou G, Coppée JY, Ghigo JM, Beloin C (2013) Starvation, together with the SOS response, mediates high biofilm-specific tolerance to the fluoroquinolone ofloxacin. PLoS Genet 9(1):e1003144. doi:10.1371/journal.pgen.1003144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Schaible B, Taylor CT, Schaffer K (2012) Hypoxia increases antibiotic resistance in Pseudomonas aeruginosa through altering the composition of multidrug efflux pumps. Antimicrob Agents Chemother 56(4):2114–2118. doi:10.1128/AAC.05574-11

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Borriello G, Werner E, Roe F, Kim AM, Ehrlich GD, Stewart PS (2004) Oxygen limitation contributes to antibiotic tolerance of Pseudomonas aeruginosa in biofilms. Antimicrob Agents Chemother 48(7):2659–2664

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Kindrachuk J, Scruten E, Attah-Poku S, Bell K, Potter A, Babiuk LA, Griebel PJ, Napper S (2011) Stability, toxicity, and biological activity of host defense peptide BMAP28 and its inversed and retro-inversed isomers. Biopolymers 96(1):14–24. doi:10.1002/bip.21441

    Article  CAS  PubMed  Google Scholar 

  18. Taylor PK, Yeung AT, Hancock RE (2014) Antibiotic resistance in Pseudomonas aeruginosa biofilms: towards the development of novel anti-biofilm therapies. J Biotechnol 191:121–130. doi:10.1016/j.jbiotec.2014.09.003

    Article  CAS  PubMed  Google Scholar 

  19. Jolivet-Gougeon A, Bonnaure-Mallet M (2014) Biofilms as a mechanism of bacterial resistance. Drug Discov Today Technol 11:49–56. doi:10.1016/j.ddtec.2014.02.003

    Article  PubMed  Google Scholar 

  20. Lewis K (2012) Persister cells: molecular mechanisms related to antibiotic tolerance. In: Coates ARM (ed) Antibiotic resistance. Handbook of experimental pharmacology, vol 211. Springer, Berlin Heidelberg, pp 121–133. doi:10.1007/978-3-642-28951-4_8

    Chapter  Google Scholar 

  21. Hu Y, Coates A (2012) Nonmultiplying bacteria are profoundly tolerant to antibiotics. In: Coates ARM (ed) Antibiotic resistance. Handbook of experimental pharmacology, vol 211. Springer, Berlin Heidelberg, pp 99–119. doi:10.1007/978-3-642-28951-4_7

    Chapter  Google Scholar 

  22. Harrison JJ, Turner RJ, Ceri H (2005) Persister cells, the biofilm matrix and tolerance to metal cations in biofilm and planktonic Pseudomonas aeruginosa. Environ Microbiol 7(7):981–994

    Article  CAS  PubMed  Google Scholar 

  23. Harrison JJ, Ceri H, Roper NJ, Badry EA, Sproule KM, Turner RJ (2005) Persister cells mediate tolerance to metal oxyanions in Escherichia coli. Microbiology 151(Pt 10):3181–3195

    Article  CAS  PubMed  Google Scholar 

  24. LaFleur MD, Qi Q, Lewis K (2010) Patients with long-term oral carriage harbor high-persister mutants of Candida albicans. Antimicrob Agents Chemother 54(1):39–44

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Spoering AL, Lewis K (2001) Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. J Bacteriol 183(23):6746–6751

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Conlon BP (2014) Staphylococcus aureus chronic and relapsing infections: evidence of a role for persister cells: an investigation of persister cells, their formation and their role in S. aureus disease. Bioessays 36(10):991–996. doi:10.1002/bies.201400080

    Article  PubMed  Google Scholar 

  27. Conlon BP, Nakayasu ES, Fleck LE, LaFleur MD, Isabella VM, Coleman K, Leonard SN, Smith RD, Adkins JN, Lewis K (2013) Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature 503(7476):365–370. doi:10.1038/nature12790

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Brötz-Oesterhelt H, Beyer D, Kroll HP, Endermann R, Ladel C, Schroeder W, Hinzen B, Raddatz S, Paulsen H, Henninger K, Bandow JE, Sahl HG, Labischinski H (2005) Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nat Med 11(10):1082–1087

    Article  PubMed  Google Scholar 

  29. Kirstein J, Hoffmann A, Lilie H, Schmidt R, Rübsamen-Waigmann H, Brötz-Oesterhelt H, Mogk A, Turgay K (2009) The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an uncontrolled protease. EMBO Mol Med 1(1):37–49. doi:10.1002/emmm.200900002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Dörr T, Vulić M, Lewis K (2010) Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biol 8(2):e1000317. doi:10.1371/journal.pbio.1000317

    Article  PubMed Central  PubMed  Google Scholar 

  31. Kim S-M, Kim HC, Lee S-WS (2011) Characterization of antibiotic resistance determinants in oral biofilms. J Microbiol 49(4):595–602

    Article  CAS  PubMed  Google Scholar 

  32. Walker CB, Tyler KZ, Low SB, King CJ (1987) Penicillin-degrading enzymes in sites associated with adult periodontitis. Oral Microbiol Immunol 2(3):129–131

    Article  CAS  PubMed  Google Scholar 

  33. Handal T, Olsen I, Walker CB, Caugant DA (2005) Detection and characterization of beta-lactamase genes in subgingival bacteria from patients with refractory periodontitis. FEMS Microbiol Lett 242(2):319–324

    Article  CAS  PubMed  Google Scholar 

  34. Handal T, Olsen I, Walker CB, Caugant DA (2004) Beta-lactamase production and antimicrobial susceptibility of subgingival bacteria from refractory periodontitis. Oral Microbiol Immunol 19(5):303–308

    Article  CAS  PubMed  Google Scholar 

  35. Handal T, Caugant DA, Olsen I (2003) Antibiotic resistance in bacteria isolated from subgingival plaque in a Norwegian population with refractory marginal periodontitis. Antimicrob Agents Chemother 47(4):1443–1446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Ciofu O, Høiby N (2007) Chapter 10. Cystic fibrosis: coping with resistance. In: Kluytmans JAJW, Diederen BMW (eds) Antibiotic policies. Fighting resistance. Springer, New York, pp 149–174

    Google Scholar 

  37. Bagge N, Schuster M, Hentzer M, Ciofu O, Givskov M, Greenberg EP, Høiby N (2004) Pseudomonas aeruginosa biofilms exposed to imipenem exhibit changes in global gene expression and β-lactamase and alginate production. Antimicrob Agents Chemother 48(4):1175–1187

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Bagge N, Hentzer M, Andersen JB, Ciofu O, Givskov M, Høiby N (2004) Dynamics and spatial distribution of β-lactamase expression in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 48(4):1168–1174

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Dibdin GH, Assinder SJ, Nichols WW, Lambert PA (1996) Mathematical model of β-lactam penetration into a biofilm of Pseudomonas aeruginosa while undergoing simultaneous inactivation by released β-lactamases. J Antimicrob Chemother 38(5):757–769

    Article  CAS  PubMed  Google Scholar 

  40. Hengzhuang W, Ciofu O, Yang L, Wu H, Song Z, Oliver A, Høiby N (2013) High β-lactamase levels change the pharmacodynamics of β-lactam antibiotics in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 57(1):196–204

    Article  PubMed Central  PubMed  Google Scholar 

  41. Klausen M, Aaes-Jørgensen A, Molin S, Tolker-Nielsen T (2003) Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol Microbiol 50(1):61–68

    Article  CAS  PubMed  Google Scholar 

  42. Haagensen JA, Klausen M, Ernst RK, Miller SI, Folkesson A, Tolker-Nielsen T, Molin S (2007) Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant cells in Pseudomonas aeruginosa biofilms. J Bacteriol 189(1):28–37

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Mah T-F (2012) Biofilm-specific antibiotic resistance. Future Microbiol 7(9):1061–1072

    Article  CAS  PubMed  Google Scholar 

  44. Van Acker H, Van Dijck P, Coenye T (2014) Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms. Trends Microbiol 22(6):326–333

    Article  PubMed  Google Scholar 

  45. Colvin KM, Irie Y, Tart CS, Urbano R, Whitney JC, Ryder C, Howell PL, Wozniak DJ, Parsek MR (2012) The Pel and Psl polysaccharides provide Pseudomonas aeruginosa structural redundancy within the biofilm matrix. Environ Microbiol 14(8):1913–1928

    Article  CAS  PubMed  Google Scholar 

  46. Jefferson KK, Goldmann DA, Pier GB (2005) Use of confocal microscopy to analyze the rate of vancomycin penetration through Staphylococcus aureus biofilms. Antimicrob Agents Chemother 49(6):2467–2473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Mulcahy H, Charron-Mazenod L, Lewenza S (2008) Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog 4(11):e1000213

    Article  PubMed Central  PubMed  Google Scholar 

  48. Nicas TI, Hancock RE (1980) Outer membrane protein H1 of Pseudomonas aeruginosa: involvement in adaptive and mutational resistance to ethylenediaminetetraacetate, polymyxin B, and gentamicin. J Bacteriol 143(2):872–878

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Southey-Pillig CJ, Davies DG, Sauer K (2005) Characterization of temporal protein production in Pseudomonas aeruginosa biofilms. J Bacteriol 187(23):8114–8126

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Williamson KS, Richards LA, Perez-Osorio AC, Pitts B, McInnerney K, Stewart PS, Franklin MJ (2012) Heterogeneity in Pseudomonas aeruginosa biofilms includes expression of ribosome hibernation factors in the antibiotic-tolerant subpopulation and hypoxia-induced stress response in the metabolically active population. J Bacteriol 194(8):2062–2073

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Ito A, Taniuchi A, May T, Kawata K, Okabe S (2009) Increased antibiotic resistance of Escherichia coli in mature biofilms. Appl Environ Microbiol 75(12):4093–4100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Lai S, Tremblay J, Déziel E (2009) Swarming motility: a multicellular behaviour conferring antimicrobial resistance. Environ Microbiol 11(1):126–136

    Article  CAS  PubMed  Google Scholar 

  53. Kaplan JB (2011) Antibiotic-induced biofilm formation. Int J Artif Organs 34(9):737–751

    Article  CAS  PubMed  Google Scholar 

  54. Jørgensen KM, Wassermann T, Jensen PØ, Hengzuang W, Molin S, Høiby N, Ciofu O (2013) Sublethal ciprofloxacin treatment leads to rapid development of high-level ciprofloxacin resistance during long-term experimental evolution of Pseudomonas aeruginosa. Antimicrob Agents Chemother 57(9):4215–4221. doi:10.1128/AAC.00493-13

    Article  PubMed Central  PubMed  Google Scholar 

  55. Driffield K, Miller K, Bostock JM, O’Neill AJ, Chopra I (2008) Increased mutability of Pseudomonas aeruginosa in biofilms. J Antimicrob Chemother 61(5):1053–1056. doi:10.1093/jac/dkn044

    Article  CAS  PubMed  Google Scholar 

  56. Conibear TC, Collins SL, Webb JS (2009) Role of mutation in Pseudomonas aeruginosa biofilm development. PLoS One 4(7):e6289. doi:10.1371/journal.pone.0006289

    Article  PubMed Central  PubMed  Google Scholar 

  57. Macià MD, Pérez JL, Molin S, Oliver A (2011) Dynamics of mutator and antibiotic-resistant populations in a pharmacokinetic/pharmacodynamic model of Pseudomonas aeruginosa biofilm treatment. Antimicrob Agents Chemother 55(11):5230–5237

    Article  PubMed Central  PubMed  Google Scholar 

  58. Hassett DJ, Ma JF, Elkins JG, McDermott TR, Ochsner UA, West SE, Huang CT, Fredericks J, Burnett S, Stewart PS, McFeters G, Passador L, Iglewski BH (1999) Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. Mol Microbiol 34(5):1082–1093

    Article  CAS  PubMed  Google Scholar 

  59. Shih P-C, Huang C-T (2002) Effects of quorum-sensing deficiency on Pseudomonas aeruginosa biofilm formation and antibiotic resistance. J Antimicrob Chemother 49(2):309–314

    Article  CAS  PubMed  Google Scholar 

  60. Bjarnsholt T, Jensen PØ, Burmølle M, Hentzer M, Haagensen JA, Hougen HP, Calum H, Madsen KG, Moser C, Molin S, Høiby N, Givskov M (2005) Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151(Pt 2):373–383

    Article  CAS  PubMed  Google Scholar 

  61. Olsen I, Tribble GD, Fiehn NE, Wang BY (2013) Bacterial sex in dental plaque. J Oral Microbiol 3:5. doi:10.3402/jom.v5i0.20736

    Google Scholar 

  62. Kadurugamuwa JL, Beveridge TJ (1999) Membrane vesicles derived from Pseudomonas aeruginosa and Shigella flexneri can be integrated into the surfaces of other gram-negative bacteria. Microbiology 145(Pt 8):2051–2060

    Article  CAS  PubMed  Google Scholar 

  63. Bhagwat AA, Gross KC, Tully RE, Keister DL (1996) Beta-glucan synthesis in Bradyrhizobium japonicum: characterization of a new locus (ndvC) influencing beta-(1→6) linkages. J Bacteriol 178(15):4635–4642

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Bhagwat AA, Tully RE, Keister DL (1993) Identification and cloning of a cyclic beta-(1→3), beta-(1→6)-D-glucan synthesis locus from Bradyrhizobium japonicum. FEMS Microbiol Lett 114(2):139–144

    CAS  PubMed  Google Scholar 

  65. Mah T-F, Pitts B, Pellock B, Walker GC, Stewart PS, O’Toole GA (2003) A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 426(6964):306–310

    Article  CAS  PubMed  Google Scholar 

  66. Beaudoin T, Zhang L, Hinz AJ, Parr CJ, Mah T-F (2012) The biofilm-specific antibiotic resistance gene ndvB is important for expression of ethanol oxidation genes in Pseudomonas aeruginosa biofilms. J Bacteriol 194(12):3128–3136

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Zhang L, Hinz AJ, Nadeau JP, Mah T-F (2011) Pseudomonas aeruginosa tssC1 links type VI secretion and biofilm-specific antibiotic resistance. J Bacteriol 193(19):5510–5513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Mah T-F (2012) Regulating antibiotic tolerance within biofilm microcolonies. J Bacteriol 194(18):4791–4792

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Liao J, Sauer K (2012) The MerR-like transcriptional regulator BrlR contributes to Pseudomonas aeruginosa biofilm tolerance. J Bacteriol 194(18):4823–4836

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Liao J, Schurr MJ, Sauer K (2013) The MerR-like regulator BrlR confers biofilm tolerance by activating multidrug efflux pumps in Pseudomonas aeruginosa biofilms. J Bacteriol 195(15):3352–3363

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Lynch SV, Dixon L, Benoit MR, Brodie EL, Keyhan M, Hu P, Ackerley DF, Andersen GL, Matin A (2007) Role of the rapA gene in controlling antibiotic resistance of Escherichia coli biofilms. Antimicrob Agents Chemother 51(10):3650–3658

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Zhang L, Fritsch M, Hammond L, Landreville R, Slatculescu C, Colavita A, Mah T-F (2013) Identification of genes involved in Pseudomonas aeruginosa biofilm-specific resistance to antibiotics. PLoS One 8(4):e61625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Gillis RJ, White KG, Choi K-H, Wagner VE, Schweizer HP, Iglewski BH (2005) Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 49(9):3858–3867

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Zhang L, Mah T-F (2008) Involvement of a novel efflux system in biofilm-specific resistance to antibiotics. J Bacteriol 190(13):4447–4452

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV (2015) Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 13:42–51

    Article  CAS  PubMed  Google Scholar 

  76. Alvarez-Ortega C, Olivares J, Martínez JL (2013) RND multidrug efflux pumps: what are they good for? Front Microbiol 4:7. doi:10.3389/fmicb.2013.00007

    Article  PubMed Central  PubMed  Google Scholar 

  77. Roberts AP, Mullany P (2010) Oral biofilms: a reservoir of transferable, bacterial, antimicrobial resistance. Expert Rev Anti Infect Ther 8(12):1441–1450

    Article  CAS  PubMed  Google Scholar 

  78. Römling U, Balsalobre C (2012) Biofilm infections, their resilience to therapy and innovative treatment strategies. J Intern Med 272(6):541–561. doi:10.1111/joim.12004

    Article  PubMed  Google Scholar 

  79. Hall-Stoodley L, Costerton JW, Stoodley P (2004) Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2(2):95–108

    Article  CAS  PubMed  Google Scholar 

  80. Lenz AP, Williamson KS, Pitts B, Stewart PS, Franklin MJ (2008) Localized gene expression in Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 74(14):4463–4471. doi:10.1128/AEM.00710-08

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Drenkard E, Ausubel FM (2002) Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416(6882):740–743

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author acknowledges Mr. Steinar Stølen for preparing Fig. 1. Funding was through a grant from the European Commission (FP7-HEALTH-306029 ‘TRIGGER’).

Conflict of interest

The author has no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Oral Biology, Faculty of Dentistry, University of Oslo, P.O. Box 1052 Blindern, Oslo, 0316, Norway

    I. Olsen

Authors
  1. I. Olsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Olsen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Olsen, I. Biofilm-specific antibiotic tolerance and resistance. Eur J Clin Microbiol Infect Dis 34, 877–886 (2015). https://doi.org/10.1007/s10096-015-2323-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-015-2323-z

Keywords

Search

Navigation