Understanding the synergistic activity of antimicrobial polymers with silver sulfadiazine

Multidrug resistant bacteria are one of the major causes of death in humans. Recently, we have investigated cationic polymers alternatives to small molecule antibiotics, to which resistance is easily acquired, and antimicrobial peptides, where poor bioavailability, high toxicity and synthetic expense hinder their clinical application. We have now identified a strong synergistic relationship between our guanidinium-containing antimicrobial polymers (GD-50) and the pre-existing antibiotic silver sulfadiazine (Ag-SD), typically applied to topical infections afflicting burn wounds. This synergistic activity suggests there is a beneficial interaction between the two compounds, enhancing combined potency by a larger-than-additive degree through a modified mechanism of action. The implications of determining the nature of this synergy are far-reaching, including allowing treatment of resistant infections, and using lower quantities of both treatments in combination to avoiding the emergence of resistance and reduce the cost of such treatments for wider accessibility. Here, we propose to use NR to gain understanding of this synergistic mechanism of action at the molecular level by determining the nature of the interaction with model of the Gram-negative inner and outer membranes.