Project Summary Copper is broadly toxic to bacteria despite being them being in contact since antiquity. Copper toxicity is seen in practice where copper surfaces and tools significantly reduce nosocomial infections and during host mediated nutritional immunity (sequestering essential metals while bombarding bacterial with toxic metals). While mechanisms of copper toxicity include Fenton chemistry and mismetallation, research is limited regarding these mechanisms are limited. Bacteria have a copper export system consisting of a repressor, a copper chaperone, and a copper exporter. The R35 this diversity supplement proposal is attached explores how bacteria, specifically Streptococcus pneumoniae evolved to interact with copper both from an effect and response point of view. Ms. Sanchez-Rosario has joined my laboratory and will work to elucidate these copper- specific mechanisms in S. pneumoniae on the side of bacterial responses.