Microbial Interactions and Pathogenesis

Methicillin resistant Staphylococcus aureus and other human pathogens including Listeria monocytogenes secrete virulence factors that help to downregulate human innate immunity thus increasing the probability of infection. The Gershenson laboratory is using a variety of biophysical techniques, particularly single molecule fluorescence spectroscopy methods, to determine how bacterial virulence factors, particularly phospholipase Cs (PLC), interact with eukaryotic cell membranes and how these interactions downregulate innate immunity. In collaboration with the Wang laboratory, the Gershenson lab discovered a novel PLC secreted by eukaryotic hosts, and showed that this enzyme processes glycosylphosphatidylinositiol (GPI)-anchored proteins on the host surface. This GPI-PLC cleaves GPI-anchored host receptors of the innate immunity system, inactivating antimicrobial responses during mutualistic host-microbe interactions. A GPI-PLC also plays a key role in compromising the capacity of humans and other susceptible mammals to control infections with African trypanosomes. The Black laboratory has shown that a Trypanosoma brucei GPI-PLC dependent process, most likely involving PLC-released glycosylinositolphosphate, co-opts natural killer cells to destroy the adaptive immune system both offering a target for chemotherapeutic arrest of pathology in trypanosomiasis and a tool that can be refined for selective depletion of lymphocyte populations in autoimmune disease. The ability of bacteria to form biofilms creates immunologically privileged niches. The bacterial chemotaxis receptor signaling proteins under investigation in the Thompson lab are representative of two component signaling systems important for processes such as biofilm formation by pathogenic microbes. The Schiffman lab engineers natural polymer structures with precise architectures — nanoparticles, fibers, ultra-thin films, and hydrogels — to encourage, diminish, and/or direct microbial cell behavior. By establishing structure-to-function relationships, as well as the investigating the materials-microbial interface, we can decrease microbial contamination without relying on antimicrobials or encouraging bacterial resistance.