Search bioRxiv⌕ Search

Biology subjects

Fernandez Salom, M. J.

Publications and source records attributed to Fernandez Salom, M. J..

2 recordsLinked to original sources

Morphological and Functional Effects of Cytoskeletal and Ion-Channel Agents on the Protoscolex of Echinococcus granulosus sensu lato

Helminthiases remain a major global health burden, and limitations of current anthelmintic therapies highlight the need for new pharmacological targets. In this study, we examined the effects of ion channel and cytoskeletal modulators on bovine lung protoscoleces (PSCs) of Echinococcus granulosus sensu lato. Compounds acting on ion channels (praziquantel, amiloride, and amlodipine) and cytoskeletal components (albendazole and cytochalasin D) were evaluated using a semi-automated motility assay, methylene blue exclusion to assess viability, and scanning electron microscopy (SEM) to characterize structural damage. All compounds produced concentration-dependent reductions in motility. Amlodipine was the most potent inhibitor of motility, whereas praziquantel and cytochalasin D produced pronounced tegumental alterations. Amiloride was the least potent compound at both endpoints and produced the mildest ultrastructural lesions. In all cases, movement was abolished at concentrations well below those required to reduce viability. Once their shared dependence on concentration was accounted for, the association between the two endpoints disappeared, indicating that paralysis and loss of viability are largely distinct responses. Motility did not recover in any compound after 24 h of drug washout. SEM analysis revealed extensive tegumental collapse, surface erosion and microtrichial loss in PSCs exposed to cytoskeletal and calcium-modulating agents. These findings highlight cytoskeletal organization and calcium-dependent ion fluxes as key physiological vulnerabilities in E. granulosus.

pharmacology and toxicology↗

Electrical Potentials of Protoscoleces of the Cestode Echinococcus granulosus from Bovine Origin

Larval stages of the tenia Echinococcus granulosus are the infective forms of cystic echinococcosis or hydatidosis, a worldwide zoonosis. The protoscolex that develops into the adult form in the definitive host is enveloped by a complex cellular syncytial tegument, where all metabolic interchange takes place. Little information is available as to the electrical activity of the parasite in this developmental stage. To gain insight into the electrical activity of the parasite at the larval stage, here we conducted microelectrode impalements of bovine lung protoscoleces (PSCs) of Echinococcus granulosus in normal saline solution. We observed two distinct intra-parasitic potentials, a transient peak potential and a stable second potential, most likely representing tegumental and intra-parasitic extracellular space electrical potential differences, respectively. These values changed upon the developmental status of the parasite, its anatomical regions, or time course after harvesting. Changes in electrical potential differences of the parasite provide an accessible and useful parameter for the study of transport mechanisms and potential targets for the development of novel antiparasitic therapeutics. Author summaryHydatid disease is a parasite-caused zoonosis that causes high morbidity and mortality and has a great impact on public health. The disease has no known cure, and the main lines of treatment include surgery and medical treatments which are not satisfactory, so new drug compounds are urgently needed. Genome sequencing of the parasite has identified different genes encoding ion channels in Echinococcus granulosus, making ion channel inhibitors a promising target for treating hydatidosis. However, no easy technical approaches are available to test the electrical contribution of ion channels to parasite physiology. In the present study, we used the microelectrode impalement technique to determine the electrical properties of the larval stages of the parasite harvested from infected cow lungs. We observed transient electrical potentials not previously reported for the parasite, and changes in these parameters associated with its developmental stage and aging. Our findings indicate that microelectrode impalement of protoscoleces of Echinococcus granulosus may be a strategy of choice to explore and test possible drugs suggested for their therapeutic potential against hydatid disease. Further evaluation of parasites coming from other animals and humans may help address important issues in the treatment and prevention of the hydatid disease.

zoology↗