Novel Antimicrobial Agents Targeting Drug Resistant Bacterial Biofilms

This project addresses two pressing problems in treating bacterial infections: the emerging resistance against current antibiotics and the role of biofilm formation in these infections.  Based on a successful lead dendrimer that acts against a broad spectrum of MDR pathogens including  A.baumannii, and MRSA in both liquid cultures and biofilms, we propose to synthesize focused libraries of mimetic compounds that retain this capability but without the peptide backbone.  A QSAR study of  antimicrobial peptide (AMP) sequences by another group suggested that appropriate patterning of nonpolar and charged groups accounts for the membrane lytic action  of many peptides. Several triazine based compounds that have been tested in previous research conform this hypothesis. Here we propose to synthesize focused libraries of monomers and oligomers to inactivate MDR strains in biofilms. Polymeric coatings for preventing film formation on  surfaces will be synthesized and evaluated in this effort. This collaboration between a company experienced in synthesizing antiviral agents and a university team with expertise in multivalent approaches to antimicrobial peptide design opens a new route to targeting membranes of MDR strains, via a mechanism that precludes development of resistance against traditional “lock-and-key” inhibition of bacterial pathways.