Rivera Research Group
Iron and Bacterial Infections
The emergence of multidrug-resistant (MDR) bacterial strains is an emerging threat to public health. Overcoming the challenges created by MDR organisms requires the identification of critical new targets and the development of small molecule inhibitors. In this context, bacterial iron metabolism offers a major vulnerability because although the concentration of free iron in the host is vanishingly small (~10-18 M), invading pathogens must obtain essential iron from the host to support their growth.
The central role of iron in infections suggests that disruption of bacterial iron acquisition paths or bacterial iron homeostasis may cause invading pathogens to lose their infectivity or be killed. Although genes that participate in these processes have designated functions, much less is known about the structure, dynamics and inter-protein associations of the proteins they code. Thus our vision is to gain atomic level understanding of key proteins and their protein-protein interactions which enable pathogens to steal heme, an abundant source of iron, and to control the concentrations of free iron in the cytosol. The structural information, in turn, is used to search for small molecule probes (inhibitors) that disrupt protein-protein interactions in vivo an in vitro. In the shorter term, the small molecules probes identified in our research are used to study bacterial metabolism and in the longer term, as possible novel antibiotics.