Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.

Küster, Tatiana; Lundström-Stadelmann, Britta; Aeschbacher, Denise; Hemphill, Andrew (2014). Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model. International journal of antimicrobial agents, 43(4), pp. 335-342. Elsevier 10.1016/j.ijantimicag.2014.01.013

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The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Küster, Tatiana; Lundström Stadelmann, Britta; Aeschbacher, Denise and Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture

ISSN:

0924-8579

Publisher:

Elsevier

Language:

English

Submitter:

Andrew Hemphill

Date Deposited:

08 Jul 2016 11:57

Last Modified:

15 Jan 2019 09:10

Publisher DOI:

10.1016/j.ijantimicag.2014.01.013

PubMed ID:

24646943

Uncontrolled Keywords:

Albendazole; Alveolar echinococcosis; Chemotherapy; Fenbendazole; Oxfendazole; Ultrastructure

BORIS DOI:

10.7892/boris.82060

URI:

https://boris.unibe.ch/id/eprint/82060

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