Dr. Katherine J. Franz, Duke University
Host: Dr. Aaron Smith
Dr. Katherine J. Franz
Duke University
Department of Chemistry
Alexander F. Hehmeyer Professor of Chemistry
April 6th, 2018 – Spring Seminar
Time and Location: Noon in Meyerhoff Chemistry, Room 120
Host: Dr. Aaron Smith
Both host cells and pathogen cells need a menu of metal nutrients for optimal growth, but also strategies to mitigate toxicity associated with misregulated or excess levels of metals like Fe, Zn, and Cu. This situation presents opportunities to manipulate cellular metals as an antimicrobial strategy. Disrupting the iron supply chain, for example, can limit microbial growth by withholding an essential pathogen nutrient. The Cu supply chain, on the other hand, requires a different approach. Cu has long been used to control microbial growth in agricultural and health care settings, and it is becoming apparent that immune cells mobilize Cu to intensify pathogen killing, while pathogens enhance Cu resistance mechanisms for their survival and virulence. We hypothesized that appropriately designed small molecules could leverage the unique copper biology occurring at the host-pathogen interface as a way to target antimicrobial agents specifically to pathogens without disturbing host cells or commensal microbiota. Here I will discuss progress we have made in identifying chemical properties that endow small molecules with the ability to synergize with Cu for toxicity, as well as strategies for targeting these agents against specific fungal and bacterial pathogens.