Guarnaschelli Inés, Koziol Uriel
Sección Biología Celular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
PLoS Pathog. 2025 Jun 4;21(6):e1013221. doi: 10.1371/journal.ppat.1013221. eCollection 2025 Jun.
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.
寄生扁虫，如绦虫和吸虫，被一种称为皮层的合胞体组织所覆盖。它由一层浅表的细胞质带（远端皮层）组成，该细胞质带通过细胞质桥与多个位于基膜下方并含有细胞核的细胞体（胞核）相连。我们对模式绦虫中殖孔绦虫的皮层细胞骨架进行了表征，并确定了阿苯达唑和阿苯达唑亚砜对其结构的影响。已知这些驱虫药靶向蠕虫中的β-微管蛋白，并且它们的作用已在线虫中得到广泛研究，但在寄生扁虫中受影响的具体细胞和组织尚不清楚。使用检测不同微管蛋白亚基和翻译后修饰的抗体，我们发现远端皮层中的微管具有独特的结构，微管束从细胞质桥放射状排列，这表明其在细胞内运输中起作用。相比之下，远端皮层中基本没有肌动蛋白丝。皮层微管对低浓度、与化疗相关的阿苯达唑和阿苯达唑亚砜具有特异性敏感性。这与胞核中分泌物质的积累相关，并且低浓度的阿苯达唑强烈降低了通过代谢标记测定的远端皮层中新合成蛋白质的掺入。出乎意料的是，阿苯达唑还导致蛋白质合成的整体下降，这与未折叠蛋白反应的激活无关。我们的工作确定皮层是绦虫中苯并咪唑类药物的敏感靶点，并表明翻译抑制可能有助于苯并咪唑类药物的驱虫作用。
