Biofilms and Their Potential Role in Wound Healing

Steven L. Percival, PhD; Philip G. Bowler, MPhil


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).



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