Fig 1.
Intracellular Salmonella adapts its metabolism to M1- and M2-polarized macrophages.
M1-type macrophages perform anaerobic glycolysis to avoid diverting oxygen from NADPH oxidase activity. Salmonella takes up fatty acids from the Salmonella-containing vacuole through the FadL transporter and degrades them through β-oxidation. The type III secretion system effector SteE drives M2 polarization. M2-type macrophages perform an oxidative metabolism. Inside M2-type macrophages, Salmonella utilizes sugars. Uptake of sugars is mediated by phosphotransferase systems (PtsG, ManXYZ) and possibly other transport systems.
Fig 2.
S. Typhimurium utilizes inflammation-derived electron acceptors and exploits host energy metabolism.
During homeostasis (left panel), microbial fermentation of fiber results in the accumulation of short chain fatty acids, such as butyrate. Butyrate instructs intestinal epithelial cells to perform β-oxidation. This oxidative host metabolism depletes oxygen at the epithelial interface. During Salmonella infection (right panel), transmigrating neutrophils introduce RNS and ROS, which give rise to tetrathionate (S4O62-) and nitrate (NO3-) in the lumen. Furthermore, inflammation depletes butyrate-producing bacteria, and the intestinal epithelium shifts to lactate fermentation. Lack of local oxygen consumption results in oxygen diffusing into the otherwise anaerobic gut lumen. Oxygen, tetrathionate, and nitrate are used by Salmonella as terminal electron acceptors to support an oxidative central metabolism. An oxidative metabolism allows for the efficient degradation of poorly fermentable carbon compounds, such as host-derived lactate. ROS, reactive oxygen species; RNS, reactive nitrogen.