Pathogenic mycobacteria manipulate host low density lipoprotein metabolism

Foam cells are a hallmark of mycobacterial infection. Despite their importance to mycobacterial infections, the exact molecular mechanisms underpinning the conversion of macrophages to foam cells in vivo are currently unknown. Using the zebrafish embryo-Mycobacterium marinum model, we have defined a conserved role for infection-induced altered host lipid metabolism in mycobacterial pathogenesis. Depletion of LDLR, a key lipid metabolism node, decreased M. marinum burden, and corrected infection-induced altered lipid metabolism resulting in decreased LDL and a reduced rate of macrophage transformation into foam cells. Our results demonstrate a conserved role for host lipid metabolism and LDLR in mycobacterial pathogenesis.