Biofilm matrix-degrading enzymes for the treatment and prevention of S. aureus-as

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DESCRIPTION (provided by applicant): Wound infections are a major medical problem. Bacteria that colonize wounds can delay wound healing and act as a focus for secondary infections. In addition, the use of antibiotics to treat wound infections results in the rapid evolution of antibiotic-resistant strains, which further complicates treatment. Wound infections have a significant impact on health resources and costs. Bacteria that colonize wounds form adherent, multicellular communities known as biofilms. The cells in a biofilm produce an extracellular polymeric matrix that holds the cells together in a mass and firmly attaches the bacterial mass to the wounded tissue. The inherent protective nature of the biofilm matrix makes wound infections difficult to treat. The extracellular matrix of most biofilms contains polymers such as polysaccharides and DNA. Enzymes that degrade biofilm matrix polymers have been shown to inhibit biofilm formation, detach pre-formed biofilms, and sensitize pre-formed biofilms to killing by antibiotics and topical biocides in vitro. Our central hypothesis is that matrix-degrading enzymes will be useful topical agents for the prophylaxis and treatment of wound infections. The objective of the present proposal is to measure the in vivo anti-biofilm activities of two biofilm matrix-degrading enzymes, DispersinB(R) (a glycoside hydrolase) and Pulmozyme(R) (DNase I). The aims of this study are to answer the following questions: (1) Do matrix-degrading enzymes potentiate the ability of topical biocides to eradicate bacterial colonization of non-wounded skin? (2) Do matrix-degrading enzymes potentiate the ability of topical biocides to decontaminate freshly contaminated full-thickness wounds? (3) Do matrix-degrading enzymes potentiate the ability of pulse irrigation treatment to decontaminate freshly contaminated full-thickness wounds? Studies will be carried out using porcine skin colonization and wound contamination models. All experiments will be carried out using the common wound pathogen Staphylococcus aureus. Topical biocides will include povidone iodine and chlorhexidine gluconate. Major outcomes will be CFU/cm2 for skin colonization models and CFU/wound for wound contamination models. The proposed experiments are expected to lead to the development of enzyme-based topical wound care formulations for testing in human clinical trials. The use of enzymes to destroy the physical integrity of the biofilm matrix is an attractive wound treatment strategy because it may reduce or eliminate the need for conventional antibiotics.