Abstract: Brucella spp can infect almost any organ or organ system in humans and thus Brucella must adapt to different metabolic conditions encountered in these tissues. However, the local availability of carbon sources possibly used by Brucella is unclear, if not controversial. Therefore, determining the metabolic conditions within target organs of Brucella, and how these conditions are affected by the host immune response, is essential to understand how Brucella is able to cause multifocal disease. Here we show MyD88 signaling regulates host metabolism, which in turn alters the metabolic requirements for Brucella virulence. In the proposed studies, we will investigate the temporal, and tissue-specific role of MyD88 on host metabolism during brucellosis and determine the effects of MyD88-dependent metabolites on control of infection.