Targeting Echinococcus multilocularis Stem Cells by Inhibition of the Polo-Like Kinase EmPlk1

摘要: Background: Alveolar echinococcosis (AE) is a life-threatening disease caused by larvae of the fox-tapeworm Echinococcus multilocularis. Crucial to AE pathology continuous infiltrative growth parasite’s metacestode stage, which driven population somatic stem cells, called germinative cells. Current anti-AE chemotherapy using benzimidazoles ineffective in eliminating cell population, thus leading remission parasite upon therapy discontinuation. Methodology/Principal findings: We herein describe characterization EmPlk1, encoded gene emplk1, displays significant homologies members Plk1 sub-family Polo-like kinases that regulate mitosis eukaryotic demonstrate cell-specific expression emplk1 RT-PCR, transcriptomics, and situ hybridization. also show EmPlk1 can induce germinal vesicle breakdown when heterologously expressed Xenopus oocytes, indicating it an active kinase. This activity was significantly suppressed presence BI 2536, inhibitor has been tested clinical trials against cancer. Addition 2536 at concentrations as low 20 nM blocked formation vesicles from cultivated Furthermore, eliminated mature vitro, yielding tissue no longer capable proliferation. Conclusions/Significance: conclude effectively inactivates E. multilocularis cells vitro direct inhibition inducing mitotic arrest killing. Since are decisive for proliferation metastasis within host, related compounds very promising complement chemotherapy.