Although decades of studies have focused on the host-pathogen interactions between macrophages and vacuolar pathogens, very little is known about how cytosolic pathogens survive in their primary niche and how the cell protects this environment from invasion by pathogens. Consistent with this study, previous work demonstrates that cytosolic survival of Francisella spp. relies on specific metabolic adaptations during invasion of the host cytosol (10), though the same metabolic pathways were not identified in this study. This outcome was expected since L. monocytogenes and Francisella spp. likely evolved mechanisms for cytosolic survival of the same host defense through convergent evolution. Here, we show that the MK biosynthetic intermediate DHNA promotes intracellular survival of L. monocytogenes in macrophages. These findings expand upon a series of recent studies demonstrating that central metabolism is at the nexus of host pathogen interactions. Host cells monitor and modulate their central metabolism both to sense and to defend against infection, whereas pathogens must modulate their metabolism both to make use of the available nutrients and to evade detection and survive in the face of host defenses. Finally, in addition to identification of a variety of new virulence determinants for L. monocytogenes, the mutants identified in this screen provide the tools necessary to identify host restriction factors that prevent cytosolic colonization by non-cytosol-adapted pathogens.