Incorporation of a biofilm dispersion autoinducer into an antimicrobial ointment for the treatment of topical wounds

Project Summary Three species of biofilm forming bacteriaAcinetobacter baumanniiPseudomonas aeruginosa and Staphylococcus aureuswere recently identified by WHO as critical or high priority pathogens for which new antibiotics or antimicrobial treatments are urgently neededWe believe the inability to effectively prevent or treat a wide range of biofilm related chronic diseases may be overcome by using a biofilm dispersal signal as an adjunctive to conventional antimicrobial therapiesStudies in our laboratory have demonstrated that Paeruginosa produces a quorum sensing moleculecisdecenoic acidcis DAthat is responsible for autoinduction of the native dispersion response in biofilm bacteriaThis signaling molecule has been shown to induce a physiological change in bacteriacausing them to disaggregate from a biofilm and alter their physiologyrendering them more susceptible to antibioticsAdditionallycis DA has been shown to induce biofilm dispersion in a wide range of Gram negative and Gram positive bacteriaas well as fungiHere we propose to determine the degree to which cis DA can improve the anti biofilm activity of a petroleum jelly based ointment with embedded antimicrobialspolymyxin Bbacitracin and neomycinExperiments will examine the killing of preformed singleand multi species biofilmsAfter confirming that the cis DA adjunctive treatment is not toxic to human keratinocyteswe will test the effects on in vitro models of wounded and infected skinIn the final line of investigationwe will examine the efficacy and safety of the treatment in murine wound modelWe anticipate that this work will result in an antimicrobial anti biofilm formulation that will improve current treatment and prevention strategies against biofilm infections in topical wounds Project Narrative The current proposal is a request for funding to begin the early stage development of a novel adjunctive to antimicrobial treatment of biofilm infections caused by Acinetobacter baumanniiPseudomonas aeruginosaand Staphylococcus aureuspathogens for which newalternative antibiotic development has been identified as a critical or high priorityBy stimulating the innate biofilm dispersion responsethis adjunctive offers a unique and innovative antimicrobial strategy for enhancing the treatment of recalcitrant infections while generating minimal selective pressure for drug resistance