Natural Products for the Treatment of Drug Resistant Infections

The European Antimicrobial Surveillance Systems estimates that as many as 52 million people worldwide carry multi-drug resistant bacteria. Among the most prevalent and lethal of these is methicillin-resistant Staphylococcus auresus (MRSA), which now causes more deaths each year in the US than HIV/AIDS. There is a pressing need to devise new strategies to combat drug-resistant bacterial infections such as MRSA. One possible strategy is the use of multi-component treatments that target the pathogen via different mechanisms. Our research laboratory is engaged in ongoing efforts to identify mixtures of constituents from natural products (plants or endophytic fungi) that may be useful against drug resistant infections.Toward this goal, we have worked with Dr. Joseph O. Falkinham at the Virginia Polytechnic University and Dr. Rob Cannon at the University of North Carolina Greensboro to identify natural products compounds with antimicrobial activity. We also have an ongoing collaboration with Dr. Glenn Kaatz at Wayne State University to identify plant effluxpump inhibitors. Finally, we are particularly interested in compounds with anti-virulence activity, as these are less likely to lead to the development of resistance than are antimicrobial agents. Through acollaboration with Dr. Alexander Horswill at the University of Iowa, we are engaged in identifying compounds that act via quorum quenching to reduce the virulence of the pathogen. With this approach, the production of toxins by the pathogen is inhibited, enabling the host to clear the infection without pressuring the organism to become more virulent.