Fellowship for Catherine Brissette: Role of Borrelia burgdorferi Rev fibronectin binding proteins in Lyme disease

Borrelia burgdorfer/; the Lyme disease agent, is an extracellular pathogen that must adapt to both its tick vector and its vertebrate hosts. B. burgdorfericauses persistent infection that can last for the hosts' lifetime. The pathogenesis of B. burgdorferidepends on outer surface proteins that interact with the cells, extracellular matrix, and components of the hosts' immune system. I recently identified two novel fibronectinbinding proteins in B. burgdorferinamed RevA and RevS. Soth of these bacterial surface proteins are expressed during mammalian infection, yet repressed during colonization of vector ticks. I hypothesize that these unique fibronectin binding proteins are critical to the natural infectious cycle by helping B. burgdorferi interact with host tissues. I propose three Specific Aims: (1) analyze the roles of RevA and RevS during the B. burgdorferiinfectious cycle; (2) define the mechanisms involved in RevA and RevS binding to fibronectin; (3) detail the mechanisms by which B. burgdorfericontrols production of RevA and RevS. Knowledge gained from these studies will form the foundation for an R01 aimed at understanding how fibronectin-binding proteins contribute to B. burgdorferivirulence, thereby directing the development of novel therapeutic and preventative treatments for Lyme disease.