Discussion

In the blood fluke Schistosoma mansoni, the facilitated glucose transporter SGTP4 is expressed exclusively in the apical double-bilayer membranes of mammalian-resident life stages, and is surface exposed. This transporter imports glucose from the host blood to support the growth, development and reproduction of the parasite. However, the molecular mechanisms that underpin SGTP4-mediated glucose uptake are not understood. Here, through biochemical characterization/functional confocal microscopy mapping of S. mansoni Akt/Protein kinase B (PKB), we discover a crucial role for Akt/PKB signalling in this process. We find that Akt/PKB, which could be activated by molecules such as host insulin and L-arginine, was active in the tegumental layer of both schistosomules and adult worms. Blockade of Akt/PKB blunted the expression and evolution of SGTP4 at the surface of the host-invading larval parasite life-stage, and suppressed SGTP4 expression in the tegument of adult worms. Concomitant glucose uptake by the parasite was also significantly attenuated in both scenarios. These findings shed light on crucial mechanistic signalling processes that underpin the energetics of glucose uptake in schistosomes. Given that the adult worms consume their dry weight in glucose every five hours, our results highlight the potential for targeting tegumental glucose transport signalling processes for parasite elimination.