The traditional direct targeting of microbes with antibiotics is now being challenged by emergence of antibiotic resistance.

We propose to augment host immunity by enhancing the anti-microbial activity of macrophages using compounds identified in screens of a large chemical library. The team will focus on E. faecalis infection, which suppresses macrophage activation in vitro and in vivo. Combination therapies that target both microbes and host immunity should more efficiently eliminate pathogens and reduce the risk of developing drug resistance, while immune stimulants should be effective with drug-resistant bacteria such as vancomycin-resistant Enterococci (VRE)