We study Borrelia spirochetes and the diseases they cause, Lyme disease and relapsing fever. After transmission of Borrelia through bites of certain tick species, both Lyme disease and relapsing fever are characterized by the spread of bacteria via the bloodstream, which may lead to the infection of multiple organs such as the skin, heart, joints, and brain. While these pathogenic processes are not yet well understood on the molecular level, the involved virulence factors identified so far have been surface lipoproteins.

A continuing long-term project identifies lipoprotein sequence determinants, membrane protein complexes and chaperones involved in spirochete lipoprotein export. We initially used fluorescent proteins as markers for protein localization in live Borrelia cells to determine the sorting signals for surface and subsurface lipoproteins, and have just completed a project that localized the lipoproteome of the Lyme disease spirochete Borrelia burgdorferi. Using cutting-edge molecular genetics and biochemical approaches, we are now in the process of dissecting the lipoprotein export machinery in B. burgdorferi down to the structure-functional level. These studies will ultimately help in the design of novel intervention strategies for spirochetal infections.

A related research project focuses on the structure-function of the OspC/Vsp surface lipoprotein family that is shared by Lyme disease and relapsing fever Borrelia. Members of this protein family have been shown to be crucial for colonization, tissue tropism and chronic infection of mammalian hosts. The long-term research goals are to define Borrelia-host interactions by integrating functional data and structural information on the proteins involved.

The first of two highly collaborative projects with colleagues at the Univ. of Kentucky and Univ. of North Dakota uses our expertise in Borrelia proteomics to define the surface lipoproteome/host- pathogen interface of Borrelia mayonii, a new Lyme disease spirochete species discovered in 2016 in the Upper Midwest of the United States. Proteins of interest will be further investigated regarding their biological function, preventive or diagnostic potential. A second pilot project investigates the response of B. burgdorferi to antibiotics on a proteomic level.

Current Grant Support:

National Institutes of Health R21 AI113547, R21 AI129522, R03 AI133056, P30 GM1110761