Leishmania spp. synthesize a unique soluble, intracellular carbohydrate reserve material termed mannogen comprising linear chains of β-1,2-linked mannose. Mannogen oligosaccharides are constitutively synthesized and turned-over in mammalian-infective parasite stages suggesting that they have an important role in regulating metabolism and intracellular survival in the mammalian host.
We have identified a new family of glycan phosphorylases (mannosyl transferase/phosphorylases or MTPs) that regulate mannogen synthesis and degradation in vivo. Gene deletion and complementation studies indicate that all family members have non-redundant role in regulating mannogen dynamics and steady-state levels in vivo, and that regulated turnover of mannogen is essential for parasite thermotolerance and virulence. Biochemical analysis of individual MPTs in vitro reveal their unique ability to utilise both mannose-1-phosphate and GDP-mannose for the de novo synthesis of mannogen whilst also retaining canonical phosphorolytic activity. We propose that the dynamic turnover of mannogen acts as a metabolic rheostat, protecting the intracellular parasites from nutrient excess within the hostile environment of the macrophage phagolysosome.