Inhibition of AMPK activation insensu stricto limits the parasite's glucose metabolism and survival.

Abstract

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by larvae of the(s.l.) cluster. There is an urgent need to develop new drug targets and drug molecules to treat CE. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a serine/threonine protein kinase consisting of α, β, and γ subunits, plays a key role in the regulation of energy metabolism. However, the role of AMPK in regulating glucose metabolism ins.l. and its effects on parasite viability is unknown. In this study, we found that targeted knockdown of EgAMPKα or a small-molecule AMPK inhibitor inhibited the viability of(s.s.) and disrupted the ultrastructure. The results ofexperiments showed that the AMPK inhibitor had a significant therapeutic effect ons.s.-infected mice and resulted in the loss of cellular structures of the germinal layer. In addition, the inhibition of the EgAMPK/EgGLUT1 pathway limited glucose uptake and glucose metabolism functions ins.s.. Overall, our results suggest that EgAMPK can be a potential drug target for CE and that inhibition of EgAMPK activation is an effective strategy for the treatment of disease.