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.