| Summary: | The human whipworm, <i>Trichuris trichiura</i>, is estimated to infect 289.6 million people globally. Control of human trichuriasis is a particular challenge, as most anthelmintics have a limited single-dose efficacy, with the striking exception of the narrow-spectrum anthelmintic, oxantel. We recently identified a novel ACR-16-like subunit from the pig whipworm, <i>T. suis</i> which gave rise to a functional acetylcholine receptor (nAChR) preferentially activated by oxantel. However, there is no ion channel described in the mouse model parasite <i>T. muris</i> so far. Here, we have identified the ACR-16-like and ACR-19 subunits from <i>T. muris</i>, and performed the functional characterization of the receptors in <i>Xenopus laevis</i> oocytes using two-electrode voltage-clamp electrophysiology. We found that the ACR-16-like subunit from <i>T. muris</i> formed a homomeric receptor gated by acetylcholine whereas the ACR-19 failed to create a functional channel. The subsequent pharmacological analysis of the <i>Tmu</i>-ACR-16-like receptor revealed that acetylcholine and oxantel were equally potent. The <i>Tmu</i>-ACR-16-like was more responsive to the toxic agonist epibatidine, but insensitive to pyrantel, in contrast to the <i>Tsu</i>-ACR-16-like receptor. These findings confirm that the ACR-16-like nAChR from <i>Trichuris</i> spp. is a preferential drug target for oxantel, and highlights the pharmacological difference between <i>Trichuris</i> species.
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