Monocyte metabolic reprogramming promotes pro-inflammatory activity and Staphylococcus aureus biofilm clearance
Nanoparticles containing the ATP synthase inhibitor oligomycin are targeted to Fc-receptor positive monocytes with tuftsin. Upon internalization, oligomycin inhibits ATP synthase of the mitochondrial electron transport chain and induces metabolic reprogramming to shift monocyte metabolism and promote pro-inflammatory gene expression. Metabolically reprogrammed monocytes also influence MDSC metabolism. Collectively, these changes promote increased antibiotic susceptibility and clearance of established biofilm infection. ADP, adenosine diphosphate; ATP, adenosine triphosphate; Fc-Receptor, fragment crystallizable region receptor; HIF-1α, hypoxia-inducible factor 1-alpha; IL-1β, interleukin-1β; iNOS, inducible nitric oxide synthase; MDSC, myeloid-derived suppressor cell; Pi, inorganic phosphate; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α.