Abstract
Bacteria frequently form biofilms in response to stress factors that include exposure of planktonic cells to subinhibitory concentrations of antibiotics. When these attach to a surface, they switch to the biofilm mode of growth and undergo a phenotypic shift in behaviour. During this process, a large suite of genes are differentially regulated to develop a biofilm, which protect them from killing by antibiotics. This leads to the persistence of biofilm infections and the mechanisms used to protect bacteria in biofilms distinct from those that are responsible for conventional antibiotic resistance as well as tolerance. This tolerance to antibiotics is contributed to by multiple factors such as poor antibiotic penetration, nutrient limitation adaptive stress responses, slowed metabolism and the formation of persister cells. The present chapter deals with the introduction to biofilm and their mechanism to achieve antibiotic resistance as well as tolerance properties including their role in persistent infection with some advancement in biofilm research.
Keywords
- Biofilm
- Tolerance
- Persistence
- Antibiotic resistance
- Challenge in chemotherapy
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
An, D., & Parsek, M. R. (2007). The promise and peril of transcriptional profiling in biofilm communities. Current Opinion in Microbiology, 10(3), 292–296. https://doi.org/10.1016/j.mib.2007.05.011.
Anderl, J. N., Franklin, M. J., & Stewart, P. S. (2000). Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrobial Agents and Chemotherapy, 44(7), 1818–1824.
Anderson, G. G., Dodson, K. W., Hooton, T. M., & Hultgren, S. J. (2004). Intracellular bacterial communities of uropathogenic Escherichia coli in urinary tract pathogenesis. Trends in Microbiology, 12, 424–430. https://doi.org/10.1016/j.tim.2004.07.005.
Ashby, M. J., Neale, J. E., Knott, S. J., & Critchley, I. A. (1994). Effect of antibiotics on non-growing planktonic cells and biofilms of Escherichia coli. Journal of Antimicrobial Chemotherapy, 33(3), 443–452. https://doi.org/10.1093/jac/33.3.443.
Aslam, S. N., Cresswell-Maynard, T., Thomas, D. N., & Underwood, G. J. (2012). Production and characterization of the intra-and extracellular carbohydrates and polymeric substances (EPS) of three sea-ice diatom species, and evidence for a cryoprotective role for EPS. Journal of Phycology, 48(6), 1494–1509. https://doi.org/10.1111/jpy.12004.
Balaban, N. Q., Merrin, J., Chait, R., Kowalik, L., & Leibler, S. (2004). Bacterial persistence as a phenotypic switch. Science, 305, 1622–1625. https://doi.org/10.1126/science.1099390.
Baselga, R., Albizu, I., & Amorena, B. (1994). Staphylococcus aureus capsule and slime as virulence factors in ruminant mastitis. A review. Veterinary Microbiology, 39, 195–204. https://doi.org/10.1016/0378-1135(94)90157-0.
Borriello, G., Werner, E., Roe, F., Kim, A. M., Ehrlich, G. D., & Stewart, P. S. (2004). Oxygen limitation contributes to antibiotic tolerance of Pseudomonas aeruginosa in biofilms. Antimicrobial Agents and Chemotherapy, 48(7), 2659–2664. https://doi.org/10.1128/AAC.48.7.2659-2664.2004.
Branda, S. S., Chu, F., Kearns, D. B., Losick, R., & Kolter, R. (2006). A major protein component of the Bacillus subtilis biofilm matrix. Molecular Microbiology, 59(4), 1229–1238. https://doi.org/10.1111/j.1365-2958.2005.05020.x.
Carl, V. C., Graham, J. C., Underwood, J. S., & David, M. P. (2014). Ecology of intertidal microbial biofilms: Mechanisms, patterns and future research needs. Journal of Sea Research, 92, 2–5. https://doi.org/10.1016/j.seares.2014.07.003.
Chakraborty, S., Dutta, T. K., De, A., Das, M., & Ghosh, S. (2018). Impact of bacterial biofilm in veterinary medicine: An overview. International Journal of Current Microbiology and Applied Sciences, 7(04), 3228–3239. https://doi.org/10.20546/ijcmas.2018.704.366.
Chiang, W. C., Nilsson, M., Jensen, P. Ø., Høiby, N., Nielsen, T. E., Givskov, M., & Tolker-Nielsen, T. (2013). Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. Antimicrobial Agents and Chemotherapy, 57(5), 2352–2361. https://doi.org/10.1128/AAC.00001-13. Epub 2013 Mar 11.
Chimileski, S., Franklin, M. J., & Papke, R. T. (2014). Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. BMC Biology, 12, 65. https://doi.org/10.1186/s12915-014-0065-5.
Ciofu, O., Tolker-Nielsen, T., Jensen, P. Ø., Wang, H., & Høiby, N. (2014). Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients. Advanced Drug Delivery Reviews, 85, 7–23. https://doi.org/10.1016/j.addr.2014.11.017. Epub 2014 Dec 2.
Costerone, J. W., Stewart, P. S., & Greenberg, E. P. (1999). Bacterial biofilms: A common cause of persistent infections. Science, 284, 1318–1322. https://doi.org/10.1126/science.284.5418.1318.
Costerton, J. W., Lewandowski, Z., Caldwell, D. E., Korber, D. R., & Lappin-Scott, H. M. (1995). Microbial biofilms. Annual Review of Microbiology, 49(1), 711–745. https://doi.org/10.1146/annurev.mi.49.100195.003431.
Costerton, J. W., Veeh, R., & Shirtliff, M. (2003). The application of biofilm science to the study and control of chronic bacterial infections. Journal of Clinical Investigation, 112, 1466–1477. https://doi.org/10.1172/JCI20365.
Danhorn, T., & Fuqua, C. (2007). Biofilm formation by plant-associated bacteria. Annual Review of Microbiology, 61, 401–422. https://doi.org/10.1146/annurev.micro.61.080706.093316.
de Beer, D., Stoodley, P., & Lewandowski, Z. (1997). Measurement of local diffusion coefficients in biofilms by microinjection and confocal microscopy. Biotechnology and Bioengineering, 53(2), 151–158. https://doi.org/10.1002/(SICI)1097-0290(19970120)53:2<151::AID-BIT4>3.0.CO;2-N.
Donlan, R. M., & Costerton, J. W. (2002). Biofilms survival mechanisms of clinically relevant microorganisms. Clinical Microbiology Reviews, 15, 167–193. https://doi.org/10.1128/CMR.15.2.167-193.2002.
Fux, C. A., Wilson, S., & Stoodley, P. (2004). Detachment characteristics and oxacillin resistance of Staphyloccocus aureus biofilm emboli in an in vitro catheter infection model. Journal of Bacteriology, 186(14), 4486–4491. https://doi.org/10.1128/JB.186.14.4486-4491.2004.
Hall-Stoodley, L., & Stoodley, P. (2009). Evolving concepts in biofilm infections. Cellular Microbiology, 11(7), 1034–1043. https://doi.org/10.1111/j.1462-5822.2009.01323.x. Epub 2009 Apr 6.
Hall-Stoodley, L., Costerton, J. W., & Stoodley, P. (2004). Bacterial biofilms: From the natural environment to infectious diseases. Nature Reviews Microbiology, 2(2), 95–108. https://doi.org/10.1038/nrmicro821.
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(7054), 1171–1175. https://doi.org/10.1038/nature03912.
Hu, Y., & Coates, A. (2012). Nonmultiplying bacteria are profoundly tolerant to antibiotics. In A. R. M. Coates (Ed.), Antibiotic resistance (Handbook of experimental pharmacology) (Vol. 211, pp. 99–119). Berlin Heidelberg: Springer. https://doi.org/10.1007/978-3-642-28951-4-7.
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(6), 467–475. https://doi.org/10.1111/lam.12134.
Jolivet-Gougeon, A., & Bonnaure-Mallet, M. (2014). Biofilms as a mechanism of bacterial resistance. Drug Discovery Today: Technologies, 11, 49–56. https://doi.org/10.1016/j.ddtec.2014.02.003.
Joubert, L. M., Wolfaardt, G. M., & Botha, A. (2006). Microbial exopolymers link predator and prey in a model yeast biofilm system. Microbial Ecology, 52(2), 187–197. https://doi.org/10.1007/s00248-006-9063-7.
Karthik, R., Ambica, R., & Nagarathnamma, T. (2018). Study of biofilm production and antimicrobial susceptibility pattern in clinical isolates of proteus species at a tertiary care hospital. International Journal of Current Microbiology and Applied Sciences, 7(01), 574–586. https://doi.org/10.20546/ijcmas.2018.701.070.
Keren, I., Shah, D., Spoering, A., Kaldalu, N., & Lewis, K. (2004). Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. Journal of Bacteriology, 186(24), 8172–8180. https://doi.org/10.1128/JB.186.24.8172-8180.2004.
Kindrachuk, J., Scruten, E., Attah-Poku, S., Bell, K., Potter, A., Babiuk, L. A., Griebel, P. J., & 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. https://doi.org/10.1002/bip.21441.
Lazăr, V., & Chifiriuc, M. C. (2010). Medical significance and new therapeutical strategies for biofilm associated infections. Romanian Archives of Microbiology and Immunology, 69(3), 125–138. on www.researchgate.net/publication/50849066.
Leid, J. G., Willson, C. J., Shirtliff, M. E., Hassett, D. J., Parsek, M. R., & Jeffers, A. K. (2005). The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria from IFNgamma- mediated macrophage killing. Journal of Immunology, 175(11), 7512–7518. https://doi.org/10.4049/jimmunol.175.11.7512.
Lenz, A. P., Williamson, K. S., Pitts, B., Stewart, P. S., & Franklin, M. J. (2008). Localized gene expression in Pseudomonas aeruginosa biofilms. Applied and Environmental Microbiology, 74(14), 4463–4471. https://doi.org/10.1128/AEM.00710-08. Epub 2008 May 16.
Lewis, K. (2007). Persister cells, dormancy and infectious disease. Nature Reviews Microbiology, 5(1), 48–56. https://doi.org/10.1038/nrmicro1557.
Lewis, K. (2012). Persister cells: molecular mechanisms related to antibiotic tolerance. In A. R. M. Coates (Ed.), Antibiotic resistance (Handbook of experimental pharmacology) (Vol. 211, pp. 121–133). Berlin Heidelberg: Springer. https://doi.org/10.1007/978-3-642-28951-4_8.
Luppens, S. B., Reij, M. W., van der Heijden, R. W., Rombouts, F. M., & Abee, T. (2002). Development of a standard test to assess the resistance of Staphylococcus aureus biofilm cells to disinfectants. Applied and Environmental Microbiology, 68(9), 4194–4200. https://doi.org/10.1128/AEM.68.9.4194-4200.2002.
Mckenney, D. (1998). The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin. Infect Immunity, 66, 4711–4720.
Molin, S., & Tolker-Nielsen, T. (2003). Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure. Current Opinion in Biotechnology, 14(3), 255–261. https://doi.org/10.1016/S0958-1669(03)00036-3.
Monroe, D. (2007). Looking for chinks in the armor of bacterial biofilms. PLoS Biology, 5(11). https://doi.org/10.1371/journal.pbio.0050307.
Muhsin, J., Ahmad, W., Andleeb, S., Jalil, F., Nawaz, M. A., Hussain, T., Muhammad, A., Muhammad, R., & Muhammad, A. K. (2018). Bacterial biofilm and associated infections. Journal of the Chinese Medical Association, 81(1), 7–11. https://doi.org/10.1016/j.jcma.2017.07.012.
Nadell, C. D., Xavier, J. B., & Foster, K. R. (2009). The sociobiology of biofilms. FEMS Microbiology Reviews, 33(1), 206–224. https://doi.org/10.1111/j.1574-6976.2008.00150.x.
Nickel, J. C., Ruseska, I., Wright, J. B., & Costerton, J. W. (1985). Tobramycin resistance of Pseudomonas aeruginosa cells growing as a biofilm on urinary catheter material. Antimicrobial Agents and Chemotherapy, 27(4), 619–624. https://doi.org/10.1128/AAC.27.4.619.
O’Toole, G. A., & Kolter, R. (May 1998). Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: A genetic analysis. Molecular Microbiology, 28(3), 449–461. https://doi.org/10.1046/j.1365-2958.1998.00797.x.
Ojha, A. K., Baughn, A. D., & Sambandan, D. (2008). Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria. Molecular Microbiology, 69, 164–174. https://doi.org/10.1111/j.1365-2958.2008.06274.x.
Pamp, S. J., Gjermansen, M., Johansen, H. K., & 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. Molecular Microbiology, 68(1), 223–240. https://doi.org/10.1111/j.1365-2958.2008.06152.x. Epub 2008 Feb 28.
Paramasivam, N., Pandian, S. K., Kushmaro, A., Voravuthi kunchai, S., & Wilson, A. (2017). Recent advances in biofilmology and antibiofilm measures. BioMed Research International, 5409325. https://doi.org/10.1155/2017/5409325.
Parsek, M. R., & Singh, P. K. (2003). Bacterial biofilms: An emerging link to disease pathogenesis. Annual Review of Microbiology, 57, 677–701. https://doi.org/10.1146/annurev.micro.57.030502.090720.
Römling, U., & Balsalobre, C. (2012). Biofilm infections, their resilience to therapy and innovative treatment strategies. Journal of Internal Medicine, 272(6), 541–561. https://doi.org/10.1111/joim.12004. Epub 2012 Oct 29.
Savage, V. J., Chopra, I., & O’Neill, A. J. (2013). Staphylococcus aureus biofilms promote horizontal transfer of antibiotic resistance. Antimicrobial Agents and Chemotherapy, 57(4), 1968–1970. https://doi.org/10.1128/AAC.02008-12.
Schaible, B., Taylor, C. T., & Schaffer, K. (2012). Hypoxia increases antibiotic resistance in Pseudomonas aeruginosa through altering the composition of multidrug efflux pumps. Antimicrobial Agents and Chemotherapy, 56(4), 2114–2118. https://doi.org/10.1128/AAC.05574-11.
Singh, P. K., Schaefer, A. L., & Parsek, M. R. (2000). Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature, 407, 762–764. https://doi.org/10.1038/35037627.
Spoering, A. L., & Lewis, K. (2001). Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials. Journal of Bacteriology, 183(23), 6746–6751. https://doi.org/10.1128/JB.183.23.6746-6751.2001.
Stewart, P. S., & Costerton, J. W. (2001). Antibiotic resistance of bacteria in biofilms. Lancet, 358(9276), 135–138. https://doi.org/10.1016/S0140-6736(01)05321-1.
Stoodley, P., deBeer, D., & Zbigniew, L. (1994). Liquid flow in biofilm systems. Applied and Environmental Microbiology, 60(8), 2711–2716.
Suci, P. A., Mittelman, M. W., Yu, F. P., & Geesey, G. G. (1994). Investigation of ciprofloxacin penetration into Pseudomonas aeruginosa biofilms. Antimicrobial Agents and Chemotherapy, 38(9), 2125–2133. https://doi.org/10.1128/AAC.38.9.2125.
Taylor, P. K., Yeung, A. T., & Hancock, R. E. (2014). Antibiotic resistance in Pseudomonas aeruginosa biofilms: Towards the development of novel anti-biofilm therapies. Journal of Biotechnology, 191, 121–130. https://doi.org/10.1016/j.jbiotec.2014.09.003. Epub 2014 Sep 18.
Vert, M., Doi, Y., Hellwich, K. H., Hess, M., Hodge, P., Kubisa, P., Rinaudo, M., & Schué, F. (2012). Terminology for biorelated polymers and applications (IUPAC Recommendations 2012). Pure and Applied Chemistry, 84(2), 377–410. https://doi.org/10.1351/PAC-REC-10-12-04.
Vlamakis, H., Aguilar, C., Losick, R., & Kolter, R. (2008). Control of cell fate by the formation of an architecturally complex bacterial community. Genes & Development, 22(7), 945–953. https://doi.org/10.1101/gad.1645008.
Walters, M. C., Roe, F., Bugnicourt, A., Franklin, M. J., & Stewart, P. S. (2003). Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrobial Agents and Chemotherapy, 47(1), 317–323. https://doi.org/10.1128/AAC.47.1.317-323.2003.
Werner, E., Roe, F., Bugnicourt, A., Franklin, M. J., Heydorn, A., Molin, S., Pitts, B., & Stewart, P. S. (2004). Stratified growth in Pseudomonas aeruginosa biofilms. Applied and Environmental Microbiology, 70(10), 6188–6196. https://doi.org/10.1128/AEM.70.10.6188-6196.2004.
Wingender, J., & Flemming, H. C. (2010). The biofilm matrix. Nature Reviews Microbiology, 8, 623–633. https://doi.org/10.1038/nrmicro2415.
Xu, K. D., McFeters, G. A., & Stewart, P. S. (2000). Biofilm resistance to antimicrobial agents. Microbiology, 146(Pt 3), 547–549. https://doi.org/10.1099/00221287-146-3-547.
Zhang, L., & Mah, T. F. (2008). Involvement of a novel efflux system in biofilm-specific resistance to antibiotics. Journal of Bacteriology, 190(13), 4447–4452. https://doi.org/10.1128/JB.01655-07.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Srivastava, D., Srivastava, S., Singh, P.C., Kumar, A. (2019). Mechanisms of Biofilm Development, Antibiotic Resistance and Tolerance and Their Role in Persistent Infections. In: Ahmad, I., Ahmad, S., Rumbaugh, K. (eds) Antibacterial Drug Discovery to Combat MDR. Springer, Singapore. https://doi.org/10.1007/978-981-13-9871-1_5
Download citation
DOI: https://doi.org/10.1007/978-981-13-9871-1_5
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-9870-4
Online ISBN: 978-981-13-9871-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)