Jeffrey H Miller
University of California, USA
Title: Using synergies to potentiate drugs such as vancomycin in Gram negative bacteria
Biography
Biography: Jeffrey H Miller
Abstract
Vancomycin (VAN) is an effective antibiotic against certain multi-drug resistant Gram-positive pathogens, such as MRSA (methicillin-resistant Staphylococcus aureus). The large size of this glycopeptide precludes it from penetrating the outer membrane of Gram-negative cells, rendering it ineffective against Gram-negative infections. However, a very small amount of VAN does enter Gram-negative cells. We sought to exploit this small concentration by finding synergies with approved drugs. We have detected strong synergies in the Gram-negative Escherichia coli between VAN and nitrofurantoin (NIT), and also trimethoprim (TMP). Concentrations of VAN as low as 12.5 µ g/ml can display an effect with NIT and concentrations of VAN of 6.25 µ g/ml can show effects with TMP. Combinations of approved drugs that are already in use offer important advantages over screening for new drugs, as the former can be applied in a clinical setting with far less delays. We have also used synergy in pair-wise drug interactions to examine models of antibiotic mechanism of action and to understand the mechanism of synergy itself.