(135f) Acid-Transforming Chitosan (ATC)/DNA Polyplexes to Eliminate Intracellular Salmonella Typhimurium infection

Drug-resistant infectious bacteria are a pressing societal challenge with conventional antibiotics are becoming less effective at treating bacterial infections. More specifically, gram-negative intracellular infection provides an additional challenge. An innovative therapy for combating these emerging superbugs requires a paradigm-shift in therapy development. Therefore, we engineered a combinatory therapy of nanoantibiotics and gene therapy. The need for an antimicrobial material with gene delivery capabilities led to the use of chitosan as our selected polymer. Here we use acid-transforming chitosan (ATC), a derivative of chitosan with enhanced solubility and pH-responsive capabilities. We explored the antimicrobial capabilities of ATC and determined the possible mechanism for the antimicrobial efficacy of ATC and chitosan. The efficacy of the free polymer was observed against S. typhimurium, an intracellular pathogen, alone at varying pH conditions which lead to a positive correlation between pH and effects the polymer had on the microbe. Additionally, ATC/DNA polyplexes were applied to RAW 264.7 cells infected with S. typhimurium expressing GFP and resulted in a decrease in the levels of bacteria found within the cells as confirmed by flow cytometry. The study indicated the possibility of using an antimicrobial vector against difficult intracellular infections and the advantages of the multi-faceted therapeutic.