The serotonergic system in cestode parasites: their potential relevance in parasite motor control and sensing of exogenous molecules

FEDERICO CAMICIA; HUGO VACA; PARK, SANG KYU; BIVONA, AUGUSTO ERNESTO; NAIDICH, A.; PREZA, M; URIEL KOZIOL; ANA MARÍA CELENTANO; MARCHANT, JONATHAN S.; MARA C. ROSENZVIT

Buenos Aires

Jornada; II Jornadas de Microbiología Celular y Molecular; 2021

Asociación Argentina de Microbiología

Introduction: The parasitic flatworms Echinococcus granulosus sensu lato (s.l.), Hymenolepis microstoma and Mesocestoides vogae (syn. M. corti) are tapeworms belonging to different families of the class Cestoda. Echinococcus granulosus s.l. is the etiological agent of Hydatid disease, a neglected disease that affects public health and economy in Argentina and worldwide. Serotonin is probably an ancient molecule with major roles in neurochemistry and development and could play important roles in the host-parasite interaction. It could be hypothesized that Cestodes, most of them living as endoparasites, could sense serotonergic signal from the host by serotonergic receptors. Currently, the treatment for echinococcosis in humans relies on benzimidazoles. However, the emergence of resistant parasites, makes the discovery of new anthelmintic drugs an imperative need. To tackle this problem, we propose to characterize G-protein coupled receptors from cestodes as new pharmacological targets. The aim of this work was the bioinformatical characterization, function and localization of new components of the serotonergic system and the potential role in the neuromuscular function. Methods: Bioinformatics analyses suggest the existence of genes encoding for almost all the components of the serotonergic system. Using this information, a novel cDNA coding for a new 5-HT GPCR was cloned, sequenced and expressed in HEK293 cells. Intracellular levels of calcium were measured. Hyperimmune antiserum was generated against the receptor protein and confocal laser microscopy was used to study the localization of the receptor. Results: When the cell line was transfected with a gene encoding for the receptor, the calcium levels increased only in the presence of serotonin but not with of other biogenic amines. Whole mount immunofluorescence performed in the larval stage of the parasite revealed branched fibers corresponding to the nervous system of the worm. Discussion: The dataset confirms the bioinformatic analyses showing that the cloned gene codes for a new 5-HT GPCR conserved in cestodes with major roles in the nervous system of the parasite. The existence of this type of receptors could be of relevance in host-parasite interaction by parasite sensing of host serotonin. Conclusion: The molecule analyzed here is a new serotonergic receptor with a particular localization in the nervous system of the parasite. This new GPCR could be exploited at the pharmacological level to design or repurpose drugs to treat neglected diseases caused by cestode parasites.