Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of .

Abstract:

() infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host-derived lipids to maintain infection, the role of macrophage lipid processing on the bacteria’s ability to access the intracellular lipid pool remains undefined. We utilized a CRISPR-Cas9 genetic approach to assess the impact of sequential steps in fatty acid metabolism on the growth of intracellular . Our analyses demonstrate that macrophages that cannot either import, store, or catabolize fatty acids restrict growth by both common and divergent antimicrobial mechanisms, including increased glycolysis, increased oxidative stress, production of pro-inflammatory cytokines, enhanced autophagy, and nutrient limitation. We also show that impaired macrophage lipid droplet biogenesis is restrictive to replication, but increased induction of the same fails to rescue growth. Our work expands our understanding of how host fatty acid homeostasis impacts growth in the macrophage.