In vitro efficacy of the anticancer drug imatinib on Echinococcus multilocularis larvae

International Journal of Antimicrobial Agents
Sarah Hemer, Klaus Brehm

Abstract

The metacestode stage of Echinococcus multilocularis is the causative agent of alveolar echinococcosis (AE), a lethal zoonosis with very limited treatment options. Chemotherapy of AE currently employs benzimidazoles (BZs); however, these exert only a parasitostatic action in vivo and have to be given life-long. In the search for novel drug targets, we have concentrated on parasite signalling pathways. Here we report significant antiparasitic effects of imatinib, an ABL kinase inhibitor that is in clinical use to treat certain cancers. At concentrations of 25 μM, imatinib was highly effective in killing Echinococcus stem cells, metacestode vesicles and protoscoleces in vitro. Moreover, already at concentrations as low as 10 μM, imatinib significantly inhibited the formation of metacestode vesicles from parasite stem cells, inactivated 50% of vesicles after 7 days, and induced morphological alterations in the metacestode upon short-term treatment. We also demonstrate that E. multilocularis larvae express enzymes with high homology to previously identified ABL-like kinases that act as imatinib targets in Schistosoma mansoni. In particular, amino acids known to mediate the binding of imatinib to target kinases are well conserved be...Continue Reading

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Citations

Jun 6, 2014·PLoS Neglected Tropical Diseases·Andreas SchubertKlaus Brehm
Sep 17, 2013·Memórias do Instituto Oswaldo Cruz·Naftale KatzNeusa Araújo
May 23, 2015·Future Medicinal Chemistry·Verena GelmedinChristoph G Grevelding
Dec 20, 2014·Future Oncology·Zahra DorostiHossein Yousofi Darani
Dec 20, 2014·Parasite : Journal De La Société Française De Parasitologie·Andrew HemphillBruno Gottstein
Dec 20, 2014·Parasite : Journal De La Société Française De Parasitologie·Klaus Brehm, Uriel Koziol
Jul 21, 2017·PLoS Neglected Tropical Diseases·Elise M O'ConnellThomas B Nutman
Jun 17, 2020·Antimicrobial Agents and Chemotherapy·Julia A LoosAndrea C Cumino
Nov 5, 2019·Scientific Reports·Hicham HouhouSimone Haeberlein
Oct 6, 2017·The Journal of Antimicrobial Chemotherapy·Weisi WangWenbao Zhang
Feb 15, 2019·Clinical Microbiology Reviews·Hao WenDonald P McManus
Jan 8, 2021·Frontiers in Veterinary Science·Carolin M MorawietzSimone Haeberlein
Feb 26, 2020·Food and Waterborne Parasitology·Britta Lundström-StadelmannAndrew Hemphill
Mar 17, 2021·Analytical and Bioanalytical Chemistry·Annika S MokoschBernhard Spengler

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