Biofilms and Their Potential Role in Wound Healing

Author(s): 
Steven L. Percival, PhD; Philip G. Bowler, MPhil

Introduction

Traditionally, microbiologists have studied bacterial structure, function, and susceptibility using cells that have been cultured in liquid medium. In this state, bacteria exist as free-floating planktonic cells. However, it is increasingly being recognized that in their natural habitat, most bacteria grow attached to a surface.[1] The growth of large aggregates of cells on a surface encased within a three-dimensional matrix of extracellular polymers (otherwise known as extracellular polymeric substance or EPS) produced by the sessile bacteria is known as a biofilm.[2] In man, the surfaces that are available for attachment are many and varied and include skin, teeth, the respiratory tract, and intestinal mucosa (Table 1).

Given the right conditions, all bacteria can grow a biofilm. Most species of bacteria that cause infection are members of the normal microflora of humans and form biofilms at sites where they exist as harmless commensals. In this situation, biofilms are considered to play a protective and beneficial role in the host. For example, biofilms in the vagina prevent colonization by exogenous pathogens—a phenomenon known as colonization resistance—and this process is synonymous with vaginal health.[3] However, due to a selection of endogenous and exogenous factors, the microbial composition of such “healthy” biofilms can become disturbed to produce a pathogenic biofilm. This has been documented to lead to diseases, such as dental caries.[4] Staphylococci, which are members of the normal microflora of the skin, frequently form biofilms on implantable medical devices, such as intravenous catheters and hip and knee joint prostheses.[5,6,7] Similarly, Pseudomonas aeruginosa is an environmental organism that regularly causes infections in burns and other wounds and constitutes a major concern for immunocompromised individuals.[8] Pseudomonas aeruginosa is very adept at biofilm formation and readily forms such structures in the lungs of individuals with cystic fibrosis; this is associated with shortened life span of the patient.[9] Most biofilms, specifically urinary and oral biofilms, are comprised of a variety of organisms, i.e., polymicrobial. In fact, in dental plaque, more than 350 different bacterial species have been identified[10] by traditional microbiological methods, although it is likely that culturable organisms may represent as little as one percent of the total microbial population.[11]

Why can Biofilms be a Problem?

It has been estimated that biofilms are associated with 65 percent of nosocomial infections[12] and that treatment of these biofilm-associated infections costs greater than $1 billion annually in the United States.[1,13] The estimated cost of a hip replacement in the UK is £3,500, but the hospital costs associated with a subsequent infection can be as high as £30,000.[5] So why are biofilm-related infections such a problem to treat? The challenge arises as a consequence of the following several factors:

1. Biofilm bacteria are less susceptible to our immune defense system, and consequently, a biofilm-associated infection can persist for a long period of time (i.e., progress from an acute to a chronic infection). Phagocytic cells have difficulty ingesting bacteria within a biofilm due to antiphagocytic properties of the biofilm matrix.[14,15] In the absence of specific antibodies, the polysaccharide component of the biofilm matrix also blocks complement activation. If antibodies are present, the polymeric matrix generally renders them ineffective. It has been shown that the biofilm matrix is also able to inhibit chemotaxis and degranulation by polymorphonucleocytes (PMNs) and macrophages and also depress the lymphoproliferative response of monocytes to polyclonal activators.[15,16] Not only are host defenses unable to deal effectively with biofilms, but their persistence can cause tissue damage (e.g., lung tissue in cystic fibrosis).

References: 

References

1. Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM. Microbial biofilms. Annual Rev Microbiol 1995;49:711–45.
2. Watnick PI, Kolter R. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol Microbiol 1999;34:586–95.
3. Wilson M. Bacterial biofilms and human disease. Science Progress 2001;84:235–54.
4. Marsh PD, Martin MV. Oral Microbiology, Third Edition. London, UK: Chapman and Hall, 1992.
5. Habash M, Reid G. Microbial biofilms: Their development and significance for medical device-related infections. J Clin Pharmacol 1999;39:887–98.
6. Khardori N, Yassien M. Biofilms in device-related infections. J Ind Microbiol 1995;15:141–7.
7. Bayston R. Medical problems due to biofilms: Clinical impact, aetiology, molecular pathogenesis, treatment and prevention. In: Newman HN, Wilson M (eds). Dental Plaque Revisited: Oral Biofilms in Health and Disease. Cardiff, UK: BioLine, 1999:111–24.
8. Lyczak JB, Cannon CL, Pier GB. Establishment of Pseudomonas aeruginosa infection: Lessons from a versatile opportunist. Microbes Infect 2000;2:1051–60.
9. Pier GB. Peptides, Pseudomonas aeruginosa, polysaccharides and lipopolysaccharides—players in the predicament of cystic fibrosis patients. Trends Microbiol 2000;8:247–50.
10. Moore WE, Moore LV. The bacteria of periodontal diseases. Periodontol 1994;5:66–77.
11. Amann RI, Ludwig W, Schleifer KH. Phylogenetic identification and in situ detection of individual microbial cells without cultivation. Microbiol Rev 1995;59:143–69.
12. Mah T-F, O’Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends in Microbiology 2001;9:34–8.
13. Archibald LK, Gaynes RP. Hospital acquired infections in the United States: The importance of interhospital comparisons. Nosocomial Infect 1997;11:245–55.
14. Williams P. Host immune defences and biofilms. In: Wimpenny J, Nichols W, Stickler D, Lappin-Scott H (eds). Bacterial Biofilms and their Control in Medicine and Industry. Cardiff, UK: BioLine, 1994:93–6.
15. Johnson GM, Lee DA, Regelmann WE, Gray ED, Peters G, Quie PG. Interference with granulocyte function by Staphylococcus epidermidis slime. Infect Immun 1986;54:13–20.
16. Shiau AL, Wu CL. The inhibitory effect of Staphylococcus epidermidis slime on the phagocytosis of murine peritoneal macrophages is interferon independent. Microbiol Immunol 1998;42:33–40.
17. Evans RC, Holmes CJ. Effect of vancomycin hydrochloride on Staphylococcus epidermidis biofilm associated with silicone elastomer. Antimicro Agents Chemother 1987;31:889–94.
18. Lewis K. Riddle of biofilm resistance. Antimicrobial Agents Chemother 2001;45:999–1007.
19. Russell AD. Biocide use and antibiotic resistance: The relevance of laboratory findings to clinical and environmental situations. The Lancet Infectious Diseases 2003;3:794–803.
20. Lewis K. Riddle of biofilm resistance. Antimicrobial Agents and Chemotherapy 2001;45:999–1007.
21. Shigeta M, Tanaka G, Komatsuzawa H, Sugai M, Suginaka H, Usui T. Permeation of antimicrobial agents through Pseudomonas aeruginosa biofilms: A simple method. Chemotherapy (Tokyo) 1997;43:340–5.
22. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: A common cause of persistent infections. Science 1999;284:1318–22.
23. Hengge-Aronis R. Regulation of gene expression during entry into stationary phase. In: Neidhart FC, et al. (eds). Escherichia coli and Salmonella: Cellular and Molecular Biology. Washington DC: ASM Press, 1996:1497–512.
24. Brown MR, Barker J. Unexplored reservoirs of pathogenic bacteria: Protozoa and biofilms. Trends Microbiol 1999;7:46–50.
25. Davies DG, Parsek MR, Pearson JP, et al. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 1998;280:295–8.
26. Gilbert P, Das J, Foley I. Biofilms susceptibility to antimicrobials. Adv Dent Res 1997;11:160–7.
28. Maira-Litrán T, Allison DG, Gilbert P. An evaluation of the potential of the multiple antibiotic resistance operon (mar) and the multidrug efflux pump acrAB to moderate resistance towards ciprofloxacin in Escherichia coli biofilms. J Antimicrob Chemother 2000;45:789–95.
28. Serralta VW, Harrison-Balestra C, Cazzaniga AL, Davis SC, Mertz M. Lifestyles of bacteria in wounds: Presence of biofilms? WOUNDS 2001;13:29–34.
29. Bowler PG, Pickworth JJ, Lilly HA. Wound microbiology—the effect of occlusion. Presented at the American Academy of Dermatology 48th Annual Meeting, December 2–7, 1989. Poster 80.
30. Bowler PG. The 105 bacterial growth guidelines: Reassessing its clinical relevance in wound healing. Ost Wound Manag 2003;49:44–53.
31. Pellizzer G, Strazzabosco M, Presi S, et al. Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection. Diabetic Medicine 2001;18:822–7.
32. Marsh PD. Host defenses and microbial homeostasis: Role of microbial interactions. Journal of Dental Research 1989;68:1567–75.



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