Expression of TRPMPZQ in excitable cells and sensory structures throughout the Schistosoma mansoni lifecycle

Abstract

Praziquantel (PZQ) is an essential medicine used to treat schistosomiasis and other infectious diseases caused by parasitic flatworms. The parasite target of PZQ is a transient receptor potential ion channel of the melastatin subfamily, TRPMPZQ. As little is currently known about the native role of TRPMPZQ in schistosomes, we developed and validated TRPMPZQ specific antibodies to immunolocalize TRPMPZQ across various S. mansoni life cycle stages (adult worms, juvenile worms, miracidia and cercariae). TRPMPZQ was expressed in muscle, nervous tissues, as well as various sensory structures on the surface of the parasite across all these life cycle stages. In adult male worms, TRPMPZQ positive neurons innervated the oral and ventral suckers as well as sensory papillae covering the head of the worm. TRPMPZQ was also present in papillae throughout the body, and within tubercles. In a S. mansoni strain selected in the laboratory for resistance to PZQ, reduced expression and immunostaining of TRPMPZQ was apparent. In immature worms, which can recover from PZQ exposure, TRPMPZQ expression was predominantly found within the musculature compared with the neuronal localization evident in adult worms. A developmental transition of TRPMPZQ from muscle to nervous tissues during schistosome maturation was also supported from single cell RNAseq data. Because muscle buffers Ca2+ transients more effectively than neurons, the transition of TRPMPZQ away from muscle during schistosome maturation may increase the sensitivity of adult male worms to PZQ.