Abstract
Over the past three years I have worked on four projects and four proteins, all bacterial gene repressors. Three of these proteins are part of the diphtheria toxin repressor-like family, while one is unrelated. The DtxR (diphtheria toxin repressor)-like family of repressors is a widely utilized class of repressors in bacteria that act as metal ion sensors to modulate the concentration of metal ions within cells. Pathogenic bacteria acquire metal ions through the expression of virulence factors, making this repressor class interesting from a human disease perspective. In order to prove the principle of drug design for the family, a docking study was undertaken for DtxR. The docking resulted in several compounds that were tested in an in vivo activity assay, which showed that compounds H and K modulate DtxR activity. Functional studies of the DtxR homologue, MtsR (Mts repressor), were undertaken in order to further characterize the DtxR family. However, consistent results for MtsR were not found. Further expression testing of a different DtxR homologue, SirR (staphylococcal iron regulator repressor), were undertaken to facilitate structural studies. Finally, expression testing of an unrelated bacterial DNA repressor (Rot, the repressor of toxins) was undertaken. However, suitable expression conditions were not found for SirR or Rot expression.