Adaptation of Echinococcus Multilocularis to Oxidative Stress Depends on EmPDK-Mediated Metabolic Reprogramming

Alveolar echinococcosis (AE), a lethal disease caused by the parasite Echinococcus multilocularis, is characterized by tumor-like growths in a host-derived oxidative microenvironment. The mechanisms that enable the parasite to adapt its central carbon metabolism to the host's oxidative microenvironment remain poorly understood. Here, we report that oxidative stress serves as a key environmental cue that induces a profound metabolic rewiring. We identified pyruvate dehydrogenase kinase (EmPDK) as the central regulator governing this metabolic adjustment, favoring glycolysis and lactate production over oxidative phosphorylation (OXPHOS). Suppressing EmPDK activity enhances oxidative metabolism and impairs metacestode proliferation, whereas augmenting its function (via H₂O₂-induced upregulation) promotes glycolysis and growth. Reactive oxygen species (ROS) drive this metabolic reprogramming through the transcription factor EmHIF1α, forming an axis of ROS/EmHIF1α/EmPDK that modulates parasite metabolic plasticity. Our findings define EmPDK as a critical mediator of oxidative stress adaptation in E. multilocularis and support its further exploration as a candidate target for AE intervention.