Guarnaschelli, I. | Search bioRxiv

bioRxiv2026

Comparative proteomics reveals a conserved core of tegumental proteins in parasitic flatworms.

Parasitic flatworms, including cestodes and trematodes, are covered by a specialized syncytial tegument that mediates nutrient uptake and host-parasite interactions. While the tegument of trematodes has been extensively characterized, its molecular composition in cestodes remains largely unknown. In this work, we performed a comparative proteomic analysis of the tegument of three cestode species, including larval and adult stages: Hymenolepis microstoma, Mesocestoides corti (syn. M. vogae) and Echinococcus multilocularis. Using stringent enrichment criteria relative to whole-worm extracts, we identified hundreds of tegument-enriched proteins in each species. Comparative analyses revealed a conserved core of tegumental proteins shared among all three species, including members of the Tegument Allergen-Like (TAL) family, vesicular trafficking components and calcium-sensing proteins, and identified candidates for nutrient uptake activities such as glucose and nucleoside transporters. Further comparative analyses revealed a set of shared tegumental proteins with the trematode Schistosoma mansoni, including conserved proteins that are specific to parasitic flatworms, supporting the existence of a conserved ancestral tegumental proteome. Finally, we confirmed tegumental expression of several candidate genes in H. microstoma and E. multilocularis, and demonstrated regionally restricted gene expression among tegumental cytons, suggesting functional specialization within the syncytial tegument. Altogether, these results reveal an evolutionarily conserved composition of the tegument of parasitic flatworms, providing a foundation for future work targeting this critical host-parasite interface.

cell biology↗

bioRxiv2025

Albendazole specifically disrupts microtubules and protein turnover in the tegument of the cestode Mesocestoides corti

Parasitic flatworms, such as cestodes and trematodes, are covered by a syncytial tissue known as the tegument. It consists of a superficial band of cytoplasm (the distal tegument) that is connected by cytoplasmic bridges to multiple cell bodies (cytons) that lay beneath the basal lamina and contain the nuclei. We characterized the cytoskeleton of the tegument of the model cestode Mesocestoides corti and determined the effects of albendazole and albendazole sulfoxide on its organization. These anthelmintics are known to target beta-tubulin in helminths, and their effects have been extensively studied in nematodes, but the specific cells and tissues that are affected are not well understood in parasitic flatworms. Using antibodies that detect different tubulin subunits and post-translational modifications, we show that microtubules in the distal tegument have a unique organization, with bouquets of microtubules radiating from the cytoplasmic bridges, suggesting a role in intracellular traffic. In contrast, actin filaments were largely absent from the distal tegument. The microtubules of the tegument were specifically sensitive to low, chemotherapeutically relevant concentrations of albendazole and albendazole sulfoxide. This was correlated with the accumulation of secretory material in the cytons, and low concentrations of albendazole strongly reduced the incorporation of newly synthesized proteins in the distal tegument, as determined by metabolic labeling. Unexpectedly, albendazole also induced a global decrease in protein synthesis, which was independent of the activation of the unfolded protein response. Our work identifies the tegument as a sensitive target of benzimidazoles in cestodes and indicates that translational inhibition may contribute to the anthelmintic effect of benzimidazoles. Author SummaryInfections caused by cestodes, such as Echinococcus spp. and Taenia spp., pose a large burden on global human health. These parasites are covered by a very particular epidermis, a syncytial tegument, which is the only contact surface between the parasite and the host. The only chemotherapy available for these infections are benzimidazoles, such as albendazole. From work in other helminths, it is well known that beta-tubulin is the molecular target of benzimidazoles, however, the affected cells and tissues are not known in flatworms. Here, we use the model cestode Mesocestoides corti to address some basic features of the tegument such as the organization of the cytoskeleton, and the effects of therapeutically relevant concentrations of albendazole in this tissue. We found that microtubules are abundant and highly organized in the tegument, and are specifically sensitive to albendazole, in comparison with other cells and tissues. Albendazole reduced the incorporation of new proteins in the tegument and produced an unexpected overall decrease in protein synthesis, which may also be of relevance for chemotherapy. Our results indicate that the tegument is a sensitive cellular target of benzimidazoles.

cell biology↗