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.
Brucella infection causes a myriad of symptoms due to the ability of Brucella to infect almost any organ or organ system. In order to survive and multiply in different organs, Brucella must be able to adapt its metabolism to the conditions encountered in the host, and we found that changes in host metabolism alter the metabolic requirements for Brucella virulence in vivo. Here, we will investigate how changes in host metabolism affect the pathogenesis of brucellosis, which will enhance understanding of the virulence of Brucella and could also improve the future rationale design of metabolic therapeutics to brucellosis.