Efficiency of Target Larvicides is Conditioned by ABC-Mediated Transport in the Zoonotic Nematode Anisakis pegreffii [PublishAheadOfPrint]

Anisakiasis is among the most significant emerging food-borne parasitoses contracted through consumption of thermally unprocessed seafood harbouring infective Anisakis spp. larvae. The efficacy of the currently applied anthelminthic therapy in humans and in model organisms has not proven sufficient, so alternative solutions employing natural compounds combined with chemical inhibitors should be explored. By testing toxicity of the natural monoterpenes nerolidol and farnesol, and conventional anthelminthics abamectin and levamisole, in the presence/absence of MK-571 and Valspodar that inhibit the ABC transporter proteins Multidrug Resistance Protein (MRP-like) and P-glycoprotein (P-gp), we determined the preliminary traits of Anisakis detoxifying mechanisms. We found that Anisakis P-gp and MRP-like transporters have a role in the efflux of the tested compounds, which could be useful in the design of novel anthelminthic strategies. Expectedly, transporter activation and efflux fluctuated over time; they were synchronously active very early post-exposure, while the activity of one transporter dominated over the other in a time-dependent manner. MRP-like transporters dominated in the efflux of farnesol and P-gp dominated in efflux of nerolidol, while both were active in effluxing levamisole. The highest toxicity was exerted by abamectin, a P-gp inhibitor per se, also eliciting the highest oxidative stress in treated Anisakis larvae. We suggest that ß-tubulin, observed for the first time as a core element in Anisakis cuticle, might represent an important target for the tested compounds.

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