Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling

BACKGROUND: In Schistosoma mansoni, the facilitated glucose transporter SGTP4, which is expressed uniquely in the apical surface tegumental membranes of the parasite, imports glucose from host blood to support its growth, development, and reproduction. However, the molecular mechanisms that underpin glucose uptake in this blood fluke are not understood. METHODS: In this study we employed techniques including Western blotting, immunolocalization, confocal laser scanning microscopy, pharmacological assays, and RNA interference to functionally characterize and map activated Akt in S mansoni. RESULTS: We find that Akt, which could be activated by host insulin and l-arginine, was active in the tegument layer of both schistosomules and adult worms. Blockade of Akt attenuated the expression and evolution of SGTP4 at the surface of the host-invading larval parasite life-stage, and suppressed SGTP4 expression at the tegument in adults; concomitant glucose uptake by the parasite was also attenuated in both scenarios. CONCLUSIONS: These findings shed light on crucial mechanistic signaling processes that underpin the energetics of glucose uptake in schistosomes, which may open up novel avenues for antischistosome drug development.