The major goal of this project is to develop a novel host-targeting approach to treat bacterial infections and prevent the spread of antibiotic resistance. Currently, all antibiotic-based therapies against bacteria are losing battle against rapid development of resistance. Moreover, the development of novel antimicrobial agents has almost completely ceased. With the increasing resistance and lack of treatment options bacterial infections are once again becoming a serious threat to the public. As such, my research objectives are to:I-1. Engineer phagocytic immune cells to enhance their ability to uptake and kill bacteria using pharmacological and genetic approachesI-2. Characterize mechanisms of actionI-3. Establish the efficacy of the engineered immune cells usingin vivoanimal modelII-1. Develop aC. elegansmodel to study horizontal gene transfer (HGT)II-2. Assess the effect of antibiotics on the polymicrobial colonization of the C. elegans intestine and identify their effect on the organismal biologyII-3. Screen for small-molecule inhibitors of HGT usingC. elegansWhen successfully completed, each of these objectives will broaden our understanding of antibiotic resistance and will provide novel ways to target antibiotic resistant bacteria.