Monday, April 29, 2024
4/29/2024
Project Summary Most chronic infections are due to the presence of biofilm, which makes microbes exceptionally recalcitrant to treatment. In soft tissue infections, such as chronic wounds, even a combination of repeated debridement and antimicrobial/antibiotic treatment frequently fails to remove the biofilm. Consequently, chronic wound infections are considered a major global health problem with over 6.5 million people suffering from them each year just in the U.S. To combat this healthcare challenge, researchers are pursuing the therapeutic use of biofilm dispersal agents, which if effective can induce microbes to leave the safety of the biofilm, increasing their susceptibility to conventional antibiotics, antimicrobials and the immune response. However, little is known about the effects of dispersal on bacteria or the host. In this project we will investigate the risk versus reward of using biofilm dispersal to treat wound infections. Using a mouse wound model, we will determine the effects of four types of dispersal strategies on Pseudomonas aeruginosa, which is common cause of wound infections and a model organism for biofilm studies. We will determine if either active or passive in vivo dispersal strategies induce phenotypic or transcriptomic changes in P. aeruginosa that could make it more threatening to the host. We will also characterize the host response after active and passive dispersal of P. aeruginosa from mouse wounds by performing a temporal analysis of clinical biomarkers, including blood physiological and biochemical indices, cytokines, and assessing whether dispersed P. aeruginosa enters the bloodstream by inducing vascular damage that leads to increased vascular permeability. We expect these experiments to reveal the pathophysiological mechanisms of dispersal-mediated sepsis and shed new light on how P. aeruginosa responds to different types of dispersal agents. On a basic science level, we will learn more about how biofilm and dispersal relate to infection and how P. aeruginosa causes bacteremia. This investigation will also provide medically translational information for therapeutic development, including potential hazards to be expected or overcome by dispersing bacteria in vivo.
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