The human whipworm,
Trichuris trichiura, 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
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The human whipworm,
Trichuris trichiura, 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,
T. suis 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
T. muris so far. Here, we have identified the ACR-16-like and ACR-19 subunits from
T. muris, and performed the functional characterization of the receptors in
Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. We found that the ACR-16-like subunit from
T. muris formed a homomeric receptor gated by acetylcholine whereas the ACR-19 failed to create a functional channel. The subsequent pharmacological analysis of the
Tmu-ACR-16-like receptor revealed that acetylcholine and oxantel were equally potent. The
Tmu-ACR-16-like was more responsive to the toxic agonist epibatidine, but insensitive to pyrantel, in contrast to the
Tsu-ACR-16-like receptor. These findings confirm that the ACR-16-like nAChR from
Trichuris spp. is a preferential drug target for oxantel, and highlights the pharmacological difference between
Trichuris species.
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