My laboratory studies Borrelia burgdorferi, the spirochetal bacterium that causes Lyme disease. B. burgdorferi is the most common arthropod-borne infectious agent in the United States, with over 35,000 cases reported to the CDC in 2008. This number represented a 30% increase from the previous year, indicating that B. burgdorferi is a re-emerging infectious agent.

The goals of my research are to understand how B. burgdorferi causes disease and adapts to different niches it occupies by: (1) addressing the role of attachment, colonization and subsequent dissemination using newly developed genetic methodologies to inactivate genes involved in adherence ofB. burgdorferi to host tissues; and (2) understanding how B. burgdorferiresponds to oxidative stress via the function of the global regulatory protein BosR.

In regard to the first project, and in collaboration with Magnus Höök’s group, we are studying how binding by B. burgdorferi to host structures impacts the infectious process.  Our initial studies evaluated the role of the fibronectin binding protein of B. burgdorferi (BBK32) in borrelial pathogenesis. This work suggested that BBK32 is required for full virulence in the mouse animal model system of Lyme borreliosis.  Subsequent studies have focused on the borrelial decorin binding protein adhesins, DbpBA.  When the dbpBA genes are deleted from B. burgdorferi, the spirochetes are significantly attenuated in the mouse model of infection, indicating that the Dbp proteins are essential for maximum virulence of B. burgdorferi.  We are currently addressing how additional B. burgdorferi proteins affect colonization, dissemination, and persistence, as well as how they alter the host immune response, to further elucidate the importance of these borrelial proteins in Lyme pathogenesis.

For the second project, the role of the BosR oxidative stress regulator is being addressed. The BosR protein is a homologue to the PerR regulator, a protein whose activity in other bacterial systems is associated with a response to oxidative stressors.  Using both biochemical and genomic based approaches, we have identified several genes, including the lone superoxide dismutase encoded by B. burgdorferi, that are putatively regulated by BosR.  We contend that B. burgdorferi responds to the redox status of its locale and uses this, in addition to pH and temperature, as a cue to modulate gene expression in order to adapt to its environment via BosR as well as other regulatory pathways.  Along these lines, we have recently found that BosR interfaces with the Rrp2-RpoN-RpoS regulatory cascade to alter the expression of genes and the production of proteins involved in borrelial pathogenesis.  As such, BosR is critical for both physiological and pathogenic properties of B. burgdorferi.