Understanding the Bacterial Biofilm Resistance to Antibiotics and Immune Evasion

  • Surekha Challa
  • G. Mohana Sheela
  • Nageswara Rao Reddy Neelapu


Biofilm is a multicellular lifestyle for bacteria to survive in adverse environmental conditions. Biofilms withstand antibiotics, immune defenses, disinfectants, nutritional changes and high temperatures. The present chapter reviews information of biofilm and also provide insights on how biofilms are able to tolerate antibiotics and evade immune system.


Biofilm Antibiotic resistance Immune evasion 



CS and NNR are grateful to GITAM (Deemed to be University) for providing necessary facilities to carry out the research work and for extending constant support.

Authors Contribution

CS and NNR initiated the review, participated in writing and revised the manuscript.

Conflict of Interest Statement

The authors declare that there is no potential conflict of interest.


  1. 1.
    Kimberly, K., & Jefferson. (2004). What drives bacteria to produce a biofilm? FEMS Microbiology Letters, 236(2), 163–173.CrossRefGoogle Scholar
  2. 2.
    Costerton, J. W., Geesey, G. G., & Cheng, K. J. (1978). How bacteria stick. Scientific American, 238(1), 86–95.CrossRefGoogle Scholar
  3. 3.
    Donlan, R. M., & Costerton, J. W. (2002). Biofilms: Survival mechanisms of clinically relevant microorganisms. Clinical Microbiology Reviews, 15(2), 167–193.CrossRefGoogle Scholar
  4. 4.
    Yang, L., Liu, Y., Wu, H., Song, Z., Høiby, N., Molin, S., & Givskov, M. (2012). Combating biofilms. FEMS Immunology and Medical Microbiology, 65, 146–157.CrossRefGoogle Scholar
  5. 5.
    Sutherland, I. W. (2001). The biofilm matrix—An immobilized but dynamic microbial environment. Trends in Microbiology, 9, 222–227.CrossRefGoogle Scholar
  6. 6.
    Hendricks, K. J., Burd, T. A., Anglen, J. O., Simpson, A. W., Christensen, G. D., & Gainor, B. J. (2001). Synergy between Staphylococcus aureus and Pseudomonas aeruginosa in a rat model of complex orthopaedic wounds. The Journal of Bone and Joint Surgery, 83, 855–861.CrossRefGoogle Scholar
  7. 7.
    Mikamo, H., Kawazoe, K., Izumi, K., Watanabe, K., Ueno, K., & Tamaya, T. (1998). Studies on the pathogenicity of anaerobes, especially Prevotella bivia, in a rat pyometra model. Infectious Diseases in Obstetrics and Gynecology, 6, 61–65.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Mastropaolo, M. D., Evans, N. P., Byrnes, M. K., Stevens, A. M., Robertson, J. L., & Melville, S. B. (2005). Synergy in polymicrobial infections in a mouse model of type 2 diabetes. Infection and Immunity, 73, 6055–6063.CrossRefGoogle Scholar
  9. 9.
    Wolcott, R., Costerton, J. W., Raoult, D., & Cutler, S. J. (2013). The polymicrobial nature of biofilm infection. Clinical Microbiology and Infection, 19, 107–112.CrossRefGoogle Scholar
  10. 10.
    Stoodley, H. L., Stoodley, P., Kathju, S., Hoiby, N., Moser, C., Costerton, J. W., Moter, A., & Bjarnsholt, T. (2012). Towards diagnostic guidelines for biofilm-associated infections. FEMS Immunology and Medical Microbiology, 65, 127–145.CrossRefGoogle Scholar
  11. 11.
    Gristina, A. G., & Costerton, J. W. (1985). Bacterial adherence to biomaterials and tissue. The significance of its role in clinical sepsis. The Journal of Bone and Joint Surgery American, 67, 264–273.CrossRefGoogle Scholar
  12. 12.
    Song, Z., Borgwardt, L., Hoiby, N., Wu, H., Sorensen, T. S., & Borgwardt, A. (2013). Prosthesis infections after orthopedic joint replacement: The possible role of bacterial biofilms. Orthopedic Reviews (Pavia), 5, 65–71.Google Scholar
  13. 13.
    Donlan, R. M. (2001). Biofilms and device-associated infections. Emerging Infectious Diseases, 7, 277–281.CrossRefGoogle Scholar
  14. 14.
    Conway, L. J., & Larson, E. L. (2012). Guidelines to prevent catheter-associated urinary tract infection: 1980 to 2010. Heart & Lung, 41, 271–283.CrossRefGoogle Scholar
  15. 15.
    Tran, P. L., Lowry, N., Campbell, T., Reid, T. W., Webster, D. R., Tobin, E., Aslani, A., Mosley, T., Dertien, J., Colmer-Hamood, J. A., & Hamood, A. N. (2012). An organoselenium compound inhibits Staphylococcus aureus biofilms on hemodialysis catheters in vivo. Antimicrobial Agents and Chemotherapy, 56, 972–978.CrossRefGoogle Scholar
  16. 16.
    Tollefson, D. F., Bandyk, D. F., Kaebnick, H. W., Seabrook, G. R., & Towne, J. B. (1987). Surface biofilm disruption. Enhanced recovery of microorganisms from vascular prostheses. Archives of Surgery, 122, 38–43.CrossRefGoogle Scholar
  17. 17.
    Marrie, T. J., & Costerton, J. W. (1984). Morphology of bacterial attachment to cardiac pacemaker leads and power packs. Journal of Clinical Microbiology, 19, 911–914.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Santos, A. P., Watanabe, E., & Andrade, D. (2011). Biofilm on artificial pacemaker: Fiction or reality? Arquivos Brasileiros de Cardiologia, 97, e113–e120.CrossRefGoogle Scholar
  19. 19.
    Gil-Perotin, S., Ramirez, P., Marti, V., Sahuquillo, J. M., Gonzalez, E., Calleja, I., Menendez, R., & Bonastre, J. (2012). Implications of endotracheal tube biofilm in ventilator-associated pneumonia response: A state of concept. Critical Care, 16, R93.CrossRefGoogle Scholar
  20. 20.
    Fux, C. A., Quigley, M., Worel, A. M., Post, C., Zimmerli, S., Ehrlich, G., & Veeh, R. H. (2006). Biofilm-related infections of cerebrospinal fluid shunts. Clinical Microbiology and Infection, 12, 331–337.CrossRefGoogle Scholar
  21. 21.
    Dasgupta, M. K. (2002). Biofilms and infection in dialysis patients. Seminars in Dialysis, 15, 338–346.CrossRefGoogle Scholar
  22. 22.
    Donelli, G., Vuotto, C., Cardines, R., & Mastrantonio, P. (2012). Biofilm-growing intestinal anaerobic bacteria. FEMS Immunology and Medical Microbiology, 65, 318–325.CrossRefGoogle Scholar
  23. 23.
    Abdel-Hafeez, M., El-Mehallaway, N., Khalil, I., Abdallah, F., & Elnaggar, A. (2014). Microbiological profile and biofilm formation on removed intrauterine contraceptive devices from a sample of Egyptian women. The Journal of Obstetrics and Gynaecology Research, 40, 1770–1776.CrossRefGoogle Scholar
  24. 24.
    Auler, M. E., Morreira, D., Rodrigues, F. F., Abr Ao, M. S., Margarido, P. F., Matsumoto, F. E., Silva, E. G., Silva, B. C., Schneider, R. P., & Paula, C. R. (2010). Biofilm formation on intrauterine devices in patients with recurrent vulvovaginal candidiasis. Medical Mycology, 48, 211–216.CrossRefGoogle Scholar
  25. 25.
    Abidi, S. H., Sherwani, S. K., Siddiqui, T. R., Bashir, A., & Kazmi, S. U. (2013). Drug resistance profile and biofilm forming potential of Pseudomonas aeruginosa isolated from contact lenses in karachi-pakistan. BMC Ophthalmology, 13, 57.CrossRefGoogle Scholar
  26. 26.
    Rieger, U. M., Mesina, J., Kalbermatten, D. F., Haug, M., Frey, H. P., Pico, R., Frei, R., Pierer, G., Luscher, N. J., & Trampuz, A. (2013). Bacterial biofilms and capsular contracture in patients with breast implants. The British Journal of Surgery, 100, 768–774.CrossRefGoogle Scholar
  27. 27.
    Christensen, L., Breiting, V., Bjarnsholt, T., Eickhardt, S., Hogdall, E., Janssen, M., Pallua, N., & Zaat, S. A. (2013). Bacterial infection as a likely cause of adverse reactions to polyacrylamide hydrogel fillers in cosmetic surgery. Clinical Infectious Diseases, 56, 1438–1444.CrossRefGoogle Scholar
  28. 28.
    Murakami, M., Nishi, Y., Seto, K., Kamashita, Y., & Nagaoka, E. (2015). Dry mouth and denture plaque microflora in complete denture and palatal obturator prosthesis wearers. Gerodontology, 32, 188–194.CrossRefGoogle Scholar
  29. 29.
    Hoiby, N., Ciofu, O., & Bjarnsholt, T. (2010). Pseudomonas aeruginosa biofilms in cystic fibrosis. Future Microbiology, 5, 1663–1674.CrossRefGoogle Scholar
  30. 30.
    Martinez-Solano, L., Macia, M. D., Fajardo, A., Oliver, A., & Martinez, J. L. (2008). Chronic Pseudomonas aeruginosa infection in chronic obstructive pulmonary disease. Clinical Infectious Diseases, 47, 1526–1533.CrossRefGoogle Scholar
  31. 31.
    Kulka, K., Hatfull, G., & Ojha, A. K. (2012). Growth of Mycobacterium tuberculosis biofilms. Journal of Visualized Experiments, 60, e3820.Google Scholar
  32. 32.
    Percival, S. L., Hill, K. E., Williams, D. W., Hooper, S. J., Thomas, D. W., & Costerton, J. W. (2012). A review of the scientific evidence for biofilms in wounds. Wound Repair and Regeneration, 20, 647–657.CrossRefGoogle Scholar
  33. 33.
    Wessman, M., Bjarnsholt, T., Eickhardt-Sorensen, S. R., Johansen, H. K., & Homoe, P. (2015). Mucosal biofilm detection in chronic otitis media: A study of middle ear biopsies from greenlandic patients. European Archives of Oto-Rhino-Laryngology, 272, 1079–1085.CrossRefGoogle Scholar
  34. 34.
    Jain, R., & Douglas, R. (2014). When and how should we treat biofilms in chronic sinusitis? Current Opinion in Otolaryngology & Head and Neck Surgery, 22, 16–21.CrossRefGoogle Scholar
  35. 35.
    FDA, U.S. Food and Drug Administration. (2001a). FDA survey of imported fresh produce. U.S. Food and Drug Administration. Center for Food Safety and Applied Nutrition, Office of Plant and Dairy Foods and Beverages. Available from: Accessed 21 May 2018.
  36. 36.
    FDA, U.S. Food and Drug Administration. (2002). FDA issue import alert on cantaloupes from Mexico. U.S. Food and Drug Administration. Office of Public Affairs. Available from: Accessed 21 May 2018.
  37. 37.
    Sapers, G. M. (2005). Washing and sanitizing treatments for fruits and vegetables. Chapter 17. In G. M. Sapers, J. R. Gorny, & A. E. Yousef (Eds.), Microbiology of fruits and vegetables (pp. 376–387). Boca Raton: CRC Taylor & Francis.Google Scholar
  38. 38.
    Sapers, G. M., Miller, R. L., Jantschke, M., & Mattrazzo, A. M. (2000). Factors limiting the efficacy of hydrogen peroxide washes for decontamination of apples containing Escherichia coli. Journal of Food Science, 65, 529–532.CrossRefGoogle Scholar
  39. 39.
    Sapers, G. M., Miller, R. L., Annous, B. A., & Burke, A. M. (2002). Improved ant antimicrobial wash treatments for decontamination of apples. Journal of Food Science, 67, 1886–1891.CrossRefGoogle Scholar
  40. 40.
    Annous, B. A., Fratamico, P. M., & Smith, J. L. (2009). Quorum sensing in biofilms: Why bacteria behave the way they do. Journal of Food Science, 74(1), R24–R37.CrossRefGoogle Scholar
  41. 41.
    Agle, M. E. (2003). Shigella boydii 18: Characterization and biofilm formation. PhD thesis, Urbana: University of Illinois.Google Scholar
  42. 42.
    Van Laar, T. A., Chen, T., You, T., & Leung, K. P. (2015). Sublethal concentrations of carbapenems alter cell morphology and genomic expression of Klebsiella pneumoniae biofilms. Antimicrobial Agents and Chemotherapy, 59, 1707–1717.CrossRefGoogle Scholar
  43. 43.
    Lorian, V., Waluschka, A., & Kim, Y. (1982). Abnormal morphology of bacteria in the sputa of patients treated with antibiotics. Journal of Clinical Microbiology, 16, 382–386.PubMedPubMedCentralGoogle Scholar
  44. 44.
    De Andrade, J. P., de Macedo Farias, L., Ferreira, J. F., Bruna-Romero, O., da Gloria de Souza, D., de Carvalho, M. A., & Dos Santos, K. V. (2016). Sub-inhibitory concentration of piperacillin-tazobactam may be related to virulence properties of filamentous Escherichia coli. Current Microbiology, 72, 19–28.CrossRefGoogle Scholar
  45. 45.
    Kim, J. E., Kim, H. E., Hwang, J. K., Lee, H. J., Kwon, H. K., & Kim, B. I. (2008). Antibacterial characteristics of Curcuma xanthorrhiza extract on Streptococcus mutans biofilm. Journal of Microbiology, 46, 228–232.CrossRefGoogle Scholar
  46. 46.
    Montanaro, L., Poggi, A., Visai, L., Ravaioli, S., Campoccia, D., Speziale, P., & Arciola, C. R. (2011). Extracellular DNA in biofilms. The International Journal of Artificial Organs, 34, 824–831.CrossRefGoogle Scholar
  47. 47.
    Okshevsky, M., & Meyer, R. L. (2015). The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Critical Reviews in Microbiology, 41, 341–352.CrossRefGoogle Scholar
  48. 48.
    Jakubovics, N. S., Shields, R. C., Rajarajan, N., & Burgess, J. G. (2013). Life after death: The critical role of extracellular DNA in microbial biofilms. Letters in Applied Microbiology, 57, 467–475.CrossRefGoogle Scholar
  49. 49.
    Sykes, R. (2010). The 2009 garrod lecture: The evolution of antimicrobial resistance: A darwinian perspective. The Journal of Antimicrobial Chemotherapy, 65, 1842–1852.CrossRefGoogle Scholar
  50. 50.
    Jones, E. A., McGillivary, G., & Bakaletz, L. O. (2013). Extracellular DNA within a nontypeable Haemophilus influenzae-induced biofilm binds human beta defensin-3 and reduces its antimicrobial activity. Journal of Innate Immunity, 5, 24–38.CrossRefGoogle Scholar
  51. 51.
    Chiang, W. C., Nilsson, M., Jensen, P. O., Hoiby, N., Nielsen, T. E., Givskov, M., & Tolker-Nielsen, T. (2013). Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. Antimicrobial Agents and Chemotherapy, 57, 2352–2361.CrossRefGoogle Scholar
  52. 52.
    Duperthuy, M., Sjostrom, A. E., Sabharwal, D., Damghani, F., Uhlin, B. E., & Wai, S. N. (2013). Role of the Vibrio cholera matrix protein bap1 in cross-resistance to antimicrobial peptides. PLoS Pathogens, 9, e1003620.CrossRefGoogle Scholar
  53. 53.
    Kulkarni, H. M., Swamy, C. V., & Jagannadham, M. V. (2014). Molecular characterization and functional analysis of outer membrane vesicles from the antarctic bacterium Pseudomonas syringae suggest a possible response to environmental conditions. Journal of Proteome Research, 13, 1345–1358.CrossRefGoogle Scholar
  54. 54.
    Yonezawa, H., Osaki, T., Kurata, S., Fukuda, M., Kawakami, H., Ochiai, K., Hanawa, T., & Kamiya, S. (2009). Outer membrane vesicles of Helicobacter pylori tk1402 are involved in biofilm formation. BMC Microbiology, 9, 197.CrossRefGoogle Scholar
  55. 55.
    Yonezawa, H., Osaki, T., Woo, T., Kurata, S., Zaman, C., Hojo, F., Hanawa, T., Kato, S., & Kamiya, S. (2011). Analysis of outer membrane vesicle protein involved in biofilm formation of Helicobacter pylori. Anaerobe, 17, 388–390.CrossRefGoogle Scholar
  56. 56.
    Lee, J., Lee, E. Y., Kim, S. H., Kim, D. K., Park, K. S., Kim, K. P., Kim, Y. K., Roh, T. Y., & Gho, Y. S. (2013). Staphylococcus aureus extracellular vesicles carry biologically active beta-lactamase. Antimicrobial Agents and Chemotherapy, 57, 2589–2595.CrossRefGoogle Scholar
  57. 57.
    Hook, V., Funkelstein, L., Wegrzyn, J., Bark, S., Kindy, M., & Hook. (2012). Cysteine Cathepsins in the secretory vesicle produce active peptides: Cathepsin L generates peptide neurotransmitters and cathepsin B produces beta-amyloid of Alzheimer’s disease. Biochimica et Biophysica Acta, 824, 89–104.CrossRefGoogle Scholar
  58. 58.
    Parsek, M. R., & Singh, P. K. (2003). Bacterial biofilms: An emerging link to disease pathogenesis. Annual Review of Microbiology, 57, 677–701.CrossRefGoogle Scholar
  59. 59.
    Lewis, K. (2007). Persister cells, dormancy and infectious disease. Nature Reviews. Microbiology, 5, 48–56.CrossRefGoogle Scholar
  60. 60.
    Nguyen, D., Joshi-Datar, A., Lepine, F., Bauerle, E., Olakanmi, O., Beer, K., McKay, G., Siehnel, R., Schafhauser, J., Wang, Y., Britigan, B. E., & Singh, P. K. (2011). Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science, 334, 982–986.CrossRefGoogle Scholar
  61. 61.
    Mena, A., Macia, M. D., Borrell, N., Moya, B., de Francisco, T., Perez, J. L., & Oliver, A. (2007). Inactivation of the mismatch repair system in Pseudomonas aeruginosa attenuates virulence but favors persistence of oropharyngeal colonization in cystic fibrosis mice. Journal of Bacteriology, 189, 3665–3668.CrossRefGoogle Scholar
  62. 62.
    Blázquez, J. (2003). Hypermutation as a factor contributing to the acquisition of antimicrobial resistance. Clinical Infectious Diseases, 37(9), 1201–1209.CrossRefGoogle Scholar
  63. 63.
    Dörr, T., Lewis, K., & Vulić, M. (2009). SOS response induces persistence to fluoroquinolones in Escherichia coli. PLoS Genetics, 5(12), e1000760.CrossRefGoogle Scholar
  64. 64.
    Dörr, T., Vulić, M., & Lewis, K. (2010). Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biology, 8(2), e1000317.CrossRefGoogle Scholar
  65. 65.
    Boles, B. R., & Singh, P. K. (2008). Endogenous oxidative stress produces diversity and adaptability in biofilm communities. Proceedings of the National Academy of Sciences of the United States of America, 105, 12503–12508.CrossRefGoogle Scholar
  66. 66.
    Boles, B. R., Thoendel, M., & Singh, P. K. (2004). Self-generated diversity produces “insurance effects” in biofilm communities. Proceedings of the National Academy of Sciences of the United States of America, 101, 16630–16635.CrossRefGoogle Scholar
  67. 67.
    Romling, U. (2012). Cyclic di-gmp, an established secondary messenger still speeding up. Environmental Microbiology, 14, 1817–1829.CrossRefGoogle Scholar
  68. 68.
    Hoffman, L. R., D’Argenio, D. A., MacCoss, M. J., Zhang, Z., Jones, R. A., & Miller, S. I. (2005). Aminoglycoside antibiotics induce bacterial biofilm formation. Nature, 436, 1171–1175.CrossRefGoogle Scholar
  69. 69.
    Parsek, M. R., & Greenberg, E. P. (2005). Sociomicrobiology: The connections between quorum sensing and biofilms. Trends in Microbiology, 13, 27–33.CrossRefGoogle Scholar
  70. 70.
    Chua, S. L., Yam, J. K., Hao, P., Adav, S. S., Salido, M. M., Liu, Y., Givskov, M., Sze, S. K., Tolker-Nielsen, T., & Yang, L. (2016). Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. Nature Communications, 7, 10750.CrossRefGoogle Scholar
  71. 71.
    Leid, J. G. (2009). Bacterial biofilms resist key host defenses. Microbe, 4, 66e70.Google Scholar
  72. 72.
    Thurlow, L. R., Hanke, M. L., Fritz, T., Angle, A., Aldrich, A., Williams, S. H., Engebretsen, I. L., Bayles, K. W., Horswill, A. R., & Kielian, T. (2011). Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. Journal of Immunology, 186, 6585–6596.CrossRefGoogle Scholar
  73. 73.
    Leid, J. G., Shirtliff, M. E., Costerton, J. W., & Stoodley, P. (2002). Human leukocytes adhere to, penetrate, and respond to Staphylococcus aureus biofilms. Infection and Immunity, 70, 6339–6345.CrossRefGoogle Scholar
  74. 74.
    Alhede, M., Bjarnsholt, T., Givskov, M., & Alhede, M. (2014). Pseudomonas aeruginosa biofilms: Mechanisms of immune evasion. Advances in Applied Microbiology, 86, 1–40.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Surekha Challa
    • 1
  • G. Mohana Sheela
    • 2
  • Nageswara Rao Reddy Neelapu
    • 1
  1. 1.Department of Biochemistry and BioinformaticsGITAM Institute of Science, Gandhi Institute of Technology and Management (GITAM)VisakhapatnamIndia
  2. 2.Department of BiotechnologyVignan UniversityGunturIndia

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