The global transcriptional regulator CodY integrates nutrient availability into the regulation of nearly all virulence genes in Staphylococcus aureus, including those required for biofilm development. Antithetical biofilm phenotypes associated with a codY null mutation have been reported previously (some strains make more biofilm, others make less biofilm); thus, the role of CodY protein in biofilm development has remained unclear. In collaboration with Dr. Ken Bayles (Center for Staphylococcal Research at UNMC), we have been investigating the matrix properties of codY mutant biofilms. Recently, we discovered that in most clinical isolates, S. aureus CodY suppresses the production of a viscous extracellular DNA (eDNA)-based biofilm under biologically relevant flow conditions, and the formation of dense cell aggregates (clumps) during planktonic growth. Currently, we are characterizing the molecular mechanism by which CodY controls the production of the biofilm, and the potential biological significance of producing an eDNA-based biofilm as well as toxins during conditions of nutrient depletion (simulated by a codY null mutant).