Biofilm and Antimicrobial Resistance

  • Vineeta MittalEmail author


Biofilm-forming bacteria cause severe health problems in patients with implanted devices by attachment of cells to surface matrix. Antibiotics can act on planktonic bacteria more easily than biofilm bacteria. Biofilm bacteria have several mechanisms for combatting antibiotic action on them. Poor penetration of antibiotics, exopolysaccharide, eDNA in matrix degradation has a role in antibiotic resistance. Limited nutrient, slow growth, the response of adaptive stress and persister cell formation also cause multilevel protections for antibiotic resistance. Genetically horizontal gene transfer and higher mutation frequency also show a pivotal role in antimicrobial resistance in biofilm bacteria.


Biofilm Antibiotic resistance Polysaccharide Extracellular DNA Persister cells Quorum sensing Efflux pump 


  1. Anderl JN, Franklin MJ, Stewart PS (2000) Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother 44:1818–1824CrossRefGoogle Scholar
  2. Billings N, Millan M, Caldara M et al (2013) The extracellular matrix component Psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog 9:e1003526CrossRefGoogle Scholar
  3. Bjarnsholt T, Jensen PO, Burmolle M et al (2005) Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151:373–383CrossRefGoogle Scholar
  4. Bowler LL, Zhanel GG, Ball TB et al (2012) Mature Pseudomonas aeruginosa biofilms prevail compared to young biofilms in the presence of ceftazidime. Antimicrob Agents Chemother 56:4976–4979Google Scholar
  5. Chua SL, Yam JK, Hao P et al (2016) Selective labeling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. Nat Commun 7:10750CrossRefGoogle Scholar
  6. Clayton WH, Mah TF (2017) Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev 41:276–301Google Scholar
  7. Colvin KM, Gordon VD, Murakami K et al (2011) The Pel polysaccharide can serve a structural and protective role in the biofilm matrix of Pseudomonas aeruginosa. PLoS Pathog 7:e1001264CrossRefGoogle Scholar
  8. Dale JL, Cagnazzo J, Phan CQ et al (2015) Multiple roles for Enterococcus faecalis glycosyltransferases in biofilm-associated antibiotic resistance, cell envelope integrity, and conjugative transfer. Antimicrob Agents Chemother 59:4094–4105Google Scholar
  9. Fabretti F, Theilacker C, Baldassarri L, Kaczynski Z, Kropec A, Holst O, Huebner J (2006) Alanine esters of enterococcal lipoteichoic acid play a role in biofilm formation and resistance to antimicrobial peptides. Infect Immun 74(7):4164–4171Google Scholar
  10. Giwercman B, Jensen ET, Hoiby N et al (1991) Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. Antimicrob Agents Chemother 35:1008–1010Google Scholar
  11. Gross M, Cramton SE, Gotz F, Peschel A (2001) Key role of teichoic acid net charge in staphylococcus aureus colonization of artificial surfaces. Infect Immun 69(5):3423–3426Google Scholar
  12. Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O (2010) Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 35:322–332CrossRefGoogle Scholar
  13. 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 49:2467–2473Google Scholar
  14. Johnson L, Mulcahy H, Kanevets U et al (2012) Surface localized spermidine protects the Pseudomonas aeruginosa outer membrane from antibiotic treatment and oxidative stress. J Bacteriol 194:813–826CrossRefGoogle Scholar
  15. Kolpen M, Appeldorff CF, Brandt S et al (2016) Increased bactericidal activity of colistin on Pseudomonas aeruginosa biofilms in anaerobic conditions. Pathog Dis 74:ftv086Google Scholar
  16. Lewis K (2001) Riddle of biofilm resistance. Antimicrob Agents Chemother 45:999–1007CrossRefGoogle Scholar
  17. Liao J, Sauer K (2012) The MerR-like transcriptional regulator BrlR contributes to Pseudomonas aeruginosa biofilm tolerance. J Bacteriol 194(18):4823–4836Google Scholar
  18. Lynch SV, Dixon L, Benoit MR et al (2007) Role of the rapA gene in controlling antibiotic resistance of Escherichia coli biofilms. Antimicrob Agents Chemother 51:3650–3658Google Scholar
  19. Mandsberg LF, Ciofu O, Kirkby N et al (2009) Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system. Antimicrob Agents Chemother 53:2483–2491CrossRefGoogle Scholar
  20. Nechaev S, Severinov K (2008) RapA: completing the transcription cycle? Structure 16:1294–1295CrossRefGoogle Scholar
  21. Nilsson M, Rybtke M, Givskov M et al (2016) The dlt genes play a role in antimicrobial tolerance of Streptococcus mutans biofilms. Int J Antimicrob Agents 48:298–304CrossRefGoogle Scholar
  22. Paraje MG (2011) Antimicrobial resistance in biofilms. In: Méndez Vilas A (ed) Science against microbial pathogens: communicating current research and technological advances, pp 736–744Google Scholar
  23. Poole K (2011) Pseudomonas aeruginosa: resistance to the max. Front Microbiol 2:65CrossRefGoogle Scholar
  24. Popat R, Crusz SA, Messina M et al (2012) Quorum-sensing and cheating in bacterial biofilms. Proc Biol Sci 279:4765–4771CrossRefGoogle Scholar
  25. Singh R, Ray P, Das A et al (2010) Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms. J Antimicrob Chemother 65:1955–1958CrossRefGoogle Scholar
  26. Singh R, Sahore S, Kaur P et al (2016) Penetration barrier contributes to bacterial biofilm-associated resistance against only select antibiotics, and exhibits genus-, strain- and antibiotic-specific differences. Pathog Dis 74.
  27. Singh S, Singh SK, Chowdhury I, Singh R (2017) Understanding the mechanism of bacterial biofilms resistance to antimicrobial agents. Open Microbiol J 11:53–62CrossRefGoogle Scholar
  28. Stewart PS (2002) Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol 292:107–113CrossRefGoogle Scholar
  29. Stewart PS, Franklin MJ, Williamson KS et al (2015) Contribution of stress responses to antibiotic tolerance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 59:3838–3847Google Scholar
  30. Sukhodolets MV, Cabrera JE, Zhi H et al (2001) RapA, a bacterial homolog of SWI2/SNF2, stimulates RNA polymerase recycling in transcription. Gene Dev 15:3330–3341CrossRefGoogle Scholar
  31. Zhang L, Fritsch M, Hammond L, Landreville R, Slatculescu C, Colavita A, Mah TF, Hancock LE (2013) Identification of genes involved in Pseudomonas aeruginosa biofilm-specific resistance to antibiotics. PLoS ONE 8(4):e61625Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of MicrobiologyDr RMLIMSLucknowIndia

Personalised recommendations