Acute and chronic wound infections represent a significant worldwide socio-economic burden to both patients and healthcare systems. The most common bacteria that cause acute wound infections include Staphylococcus aureus, whilst this organism plus others, in particular Pseudomonas aeruginosa can cause chronic wound infections. Virulence factors, toxins, biofilm production and exoproteins secreted by bacteria within the wound bed play a major role in evading host immune response, leading to persistent infection and prolonged inflammation. These factors often result in failure of antimicrobial treatment with both systemic and topical antimicrobial agents. Hence, there is an urgent need for novel antimicrobials to treat wound infections by overcoming the factors associated with treatment failure, which over recent years has been increasingly associated with biofilm formation. Using clinical and reference strains of these organisms we propose to investigate the potential treatment of wound infections with novel treatment agents that our laboratory and others have identified over recent years as possessing significant potential in the treatment of biofilm. These treatment agents, which include an antimicrobial peptide, a fatty acid derivative and bacteriophages, will be investigated for effectiveness versus bacterial isolates in vitro. We will develop in vivo like models of wound infection in vitro and investigate the impact of these agents on inflammatory cytokines, toxicity and induction of antimicrobial resistance. Study of these agents will be extended into a porcine model of wound infection where the novel treatment agents will be reconstituted within a hydrogel, applied to the skin surface and most effective agents identified. Within the animal model, recovery of bacteria, local cytokine response, expression of virulence genes and wound healing in response to topical treatment will be investigated. Results from this study will lead to clinical trials in humans by identifying novel treatments for this very common clinical condition.
