New antibiotics with novel modes of action are necessary to combat the increasing number of drug-resistant bacteria. In recent years, very few antibiotics have been introduced due to challenges identifying new bacterial targets effective to the current and emerging resistance mechanisms. The long-term goal of this research is to develop new antimicrobial agents based on cationic methacrylate polymers. In this study, we evaluated the activity of these polymers against bacteria and their cytotoxicity to mammalian cells. The minimum inhibitory concentration (MIC) against a panel of Gram-positive and negative bacteria was determined using a standard turbidity-based assay. In general, the polymers were more active against the Gram-positive bacteria as opposed to the Gram-negative bacteria with the exception of S. enterica. The cytotoxicity of these polymers to mammalian cells was also evaluated by a cell-viability XTT assay. At high concentrations, polymers significantly reduced the cell viability of HEp-2 (IC50 = 70 �g/mL) and COS-7 cells (IC50 = 250 �g/mL). One polymer was tested against an S. aureus nasal colonization in a rat model. This polymer successfully reduced the number of S. aureus colonies in the nasal cavity by 99%, as compared to the antibiotic mupirocin (58% colony reduction).

Evaluation of selective activity and cytotoxicity of antimicrobial cationic methacrylate polymers

247th National Meeting (2014)

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