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. 2014 Oct 31;3(3):e959416.
doi: 10.4161/21624046.2014.959416. eCollection 2014 Jul-Sep.

Acquired resistance to monepantel in C. elegans: What about parasitic nematodes?

Michael Forbiteh Fru  1 , Alessandro Puoti  1
Affiliations

Acquired resistance to monepantel in C. elegans: What about parasitic nematodes?

Michael Forbiteh Fru et al. Worm. .

Abstract

In 2008, Novartis Animal Health developed a new class of anthelmintics, the amino-acetonitrile derivatives (AAD) of which monepantel is the most prominent compound. Monepantel was designed for the treatment of sheep against the parasitic nematode Haemonchus contortus. Because monepantel acts through a different mechanism, it is effective against nematodes that have acquired resistance to long-standing anthelmintics. In order to benefit from a maximum lifespan and efficacy of this new compound, the mode of action of monepantel needs to be understood. Studies on the model nematode Caenorhabditis elegans led to the identification of at least one target of monepantel: the monovalent cation channel ACR-23. Here we comment on the effects of monepantel on C. elegans and on the development of resistant parasitic nematode strains.

Keywords: C. elegans; acr-23; anthelmintic; monepantel; motility; parasite.

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Figures

Figure 1.
Figure 1.
How C. elegans could develop resistance to monepantel. The ACR-23 receptor is represented by a homopentamer that transports monovalent cations (open circles) into the cytosol. ACR-23 is activated by betaine (filled red circles) and monepantel (filled green circles). Betaine is also transported across the membrane by SNF-3. The synthesis of a functional ACR-23 receptor involves several steps, which if inactivated, could result in partial or full resistance to monepantel. Such steps involve gene expression (circled “1”) and assembly of the receptor (“3”), for example by the chaperone RIC-3. In fact, ric-3 mutants are moderately resistant to monepantel. Mutations in the ACR-23 protein result in resistance to monepantel (“2”). Additional factors could be required for a fully functional ACR-23 receptor (“4”). Blue arrows indicate the synthesis pathway of the ACR-23 receptor. “Rm” represents a putative additional receptor to monepantel. The representation of the proteins in one single membrane tract should not imply that they are expressed in the same cell.
See this image and copyright information in PMC

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