McKinney:Metabolism

The term “parasite” is derived from the Greek parasitos, meaning, “One who eats at another’s table.” This definition underscores a central but poorly understood feature of the parasitic lifestyle: the exploitation of the host as a substrate to fuel the pathogen’s metabolism and growth. We have undertaken a systematic analysis of the in vivo metabolism of M. tuberculosis. Our analysis to date indicates that mycobacteria switch to a diet of fatty acids at late stages of infection in vivo. This switch is triggered by the host-immune response, and mutant bacteria that cannot make the switch fail to persist. One of the pathways involved, the glyoxylate cycle, is an attractive target for drug development because it is absent in human cells. Current efforts are focused on elucidation of the host mechanism that forces the switch in bacterial metabolism and on development of glyoxylate cycle inhibitors as potential anti-TB drugs.