Fumuso Fernanda G, Clement Jason A, Todd Matthew J, O'Connor Roberta M
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA.
Baruch S. Blumberg Institute, Doylestown, PA, 18902, USA.
Int J Parasitol Drugs Drug Resist. 2025 Apr 14;28:100591. doi: 10.1016/j.ijpddr.2025.100591.
Toxoplasmosis is a worldwide parasitic disease caused by the apicomplexan Toxoplasma gondii. Severe neurological illness occurs in immunosuppressed patients, and congenital disorders can follow transplacental primo infection during pregnancy. New effective antiparasitic drugs are needed since chronic cystic stages are resistant to current available treatments, and some of the congenital infections are unresponsive to available therapeutics. Tartrolon E (trtE) is a marine secondary metabolite that has high selectivity against human and animal apicomplexan parasites including T. gondii, Cryptosporidium parvum and Plasmodium falciparum. We evaluated the effect of the compound on extracellular tachyzoite viability, morphology, membrane permeability and its ability to block host cell attachment and/or invasion. While 80 % of T. gondii infective capacity is blocked after only 30 min of compound treatment, parasite viability, morphology, membrane integrity and host cell attachment were unaffected until after 4 h of treatment. These effects were irreversible when parasites were allowed to infect host cells after trtE treatment. Drug exposure for more than 4 h significantly affected tachyzoite survival and altered parasite morphology. The mechanism of action of trtE is still unknown but includes blocking parasite invasion processes. Further research is needed to determine the molecular target of trtE to further progress the compound as an antiparasitic candidate.
弓形虫病是一种由顶复门原虫刚地弓形虫引起的全球性寄生虫病。严重的神经系统疾病发生在免疫抑制患者中，先天性疾病可在孕期经胎盘初次感染后出现。由于慢性包囊阶段对现有治疗有抗性，且一些先天性感染对现有治疗无反应，因此需要新的有效抗寄生虫药物。塔尔曲洛醇E（trtE）是一种海洋次生代谢产物，对包括刚地弓形虫、微小隐孢子虫和恶性疟原虫在内的人和动物顶复门寄生虫具有高选择性。我们评估了该化合物对细胞外速殖子活力、形态、膜通透性及其阻断宿主细胞附着和/或入侵能力的影响。仅用该化合物处理30分钟后，80%的刚地弓形虫感染能力就被阻断，但直到处理4小时后，寄生虫的活力、形态、膜完整性和宿主细胞附着才受到影响。当trtE处理后的寄生虫被允许感染宿主细胞时，这些影响是不可逆的。药物暴露超过4小时会显著影响速殖子存活并改变寄生虫形态。trtE的作用机制仍然未知，但包括阻断寄生虫入侵过程。需要进一步研究以确定trtE的分子靶点，从而使该化合物作为抗寄生虫候选药物取得进一步进展。
