Biofilms and Their Potential Role in Wound Healing
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Contact with a surface triggers the expression of a panel of bacterial enzymes that catalyze the formation of sticky polymers that promote colonization and protection. The structure of biofilms is such that immune responses may be directed only at those antigens found on the outer surface of the biofilm, and antibodies and other serum proteins often fail to penetrate into the biofilm. In addition, PMNs are unable to effectively engulf bacteria growing within a complex polymer matrix attached to a solid surface. This causes the PMNs to release large amounts of pro-inflammatory enzymes and cytokines, leading to chronic inflammation and destruction of nearby tissues (i.e., chronic inflammation). Bacteria that may be embedded within the wound biofilm matrix are likely to be resistant to both immunological and non-specific defense mechanisms of the body.
2. Biofilms display innate resistance to antimicrobial agents, thus protecting associated bacteria. The reasons for this are not clear, but it is likely that antimicrobial agents are readily inactivated or fail to penetrate into the biofilm. Bacteria within biofilms may be up to 1,000 times more resistant to antimicrobial agents than those in a planktonic state.
3. Biofilms increase the opportunity for gene transfer between and among bacteria. This is important, since bacteria resistant to antibiotics may transfer the genes for resistance to neighboring susceptible bacteria. Also, gene transfer could convert a previous avirulent commensal organism into a highly virulent pathogen.
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. 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.
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