Biofilms and Their Potential Role in Wound Healing

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


Wounds. 2004;16(7) 

In This Article

Antibiotic Resistance

Antibiotics are used to treat bacterial infections. However, biofilm-related infections do not succumb so easily to this form of treatment, because they provide a protective mechanism that renders bacterial cells less susceptible to both antibiotics and biocides. However, on removal of these cells from the matrix of the biofilm, they are equally susceptible to biocides.[19] There have been a number of models used to determine resistance in biofilms, and the results of these studies have highlighted a number of the factors thought to contribute to the ability of a biofilm to tolerate high concentrations of antibiotics. These include:

  1. Impaired penetration of an antibiotic into the biofilm matrix.[20,21] Many researchers have investigated the possible lack of antibiotic/biocide penetration as an explanation of biofilm resistance. It was suggested that the antimicrobial agent either reacted chemically with the extracellular components of the biofilm or attached to the anionic polysaccharides. However, since the exopolymer matrix does not form a complete impenetrable barrier to antimicrobial agents, other mechanisms must exist within biofilms aiding bacterial survival.

  2. Reduced growth rate of bacteria in biofilms, which renders them less susceptible to antibiotics (they change from being physiologically active in the planktonic state to sessile in the biofilm state). Antibiotics are more effective in killing cells when they are growing actively. Antibiotics, such as ampicillin and penicillin, are not able to kill nongrowing cells.[22] Cephalosporins and fluoroquinolones, however, are able to kill nongrowing cells but are nonetheless more effective in killing cells that are rapidly growing and dividing. Therefore, evidence of bacteria that are growing slowly in a biofilm may contribute to reduced susceptibility to antibiotics.[22]

  3. Altered micro-environment within the biofilm (e.g., pH, oxygen content), which reduces the activity of an antimicrobial agent. There is evidence of gradients of physiological activity within a biofilm in response to antibiotic treatment.[23] This would suggest that the response to antibiotics will vary according to the location of specific cells within a biofilm ecosystem.

  4. Altered gene expression. Altered gene expression by organisms within a biofilm or a general stress response of a biofilm have been documented as factors known to reduce susceptibility to antibiotics.[24]

  5. Quorum sensing (QS). QS has been documented as being involved in antibiotic resistance, but its role is currently unclear, which justifies the need for additional research in this area.[25] QS involves the production of signalling molecules within a bacterial population that enables bacteria to communicate with each other and initiate a response to their surrounding environment once a critical population density (quorum) has been reached. In a wound environment, many different bacteria live together in often dense populations, and this provides an ideal situation for QS to occur. Communication in this way allows bacteria to coordinate their behavior and, if necessary, change physiologically to enable them to adapt to a new environment (e.g., a wound). Adaptive responses of bacteria within a wound environment may be associated with nutrient availability, competition with other microorganisms, and the avoidance of host defense mechanisms. Adaptation to a wound environment via QS may involve bacteria secreting protective EPS and increasing the production of enzymes that facilitate their tissue invasion.

  6. Reduced biofilm-specific phenotype. It has been suggested that a biofilm-specific phenotype may be induced in a subpopulation of the biofilm.[26] These subpopulations have been shown to express active mechanisms to reduce the efficacy of antibiotics.[26,27]


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