Whitta Saffron T G, Lamont Bridget, Suwanarusk Rossarin, Russell Bruce M, Muhsin-Sharafaldine Morad-Rémy
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Department of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, Thailand.
Front Microbiol. 2024 Oct 4;15:1463457. doi: 10.3389/fmicb.2024.1463457. eCollection 2024.
This study evaluated the effectiveness of anti-cryptosporidial agents nitazoxanide, halofuginone, the pyrazolopyridine analog KDU731, and paromomycin (PMC) in combating the significant zoonotic pathogen . The study utilized HCT-8 host cells to culture and fluorescent microscopy/quantitative PCR (qPCR) for detecting parasitic growth. The efficacy of the compounds was assessed by calculating their inhibitory concentrations (IC) against the total growth of at 48 h post-infection. The study further investigated the impact of these compounds on early parasitophorous vacuole (PV) formation, merozoite egress, host cell viability, and cell growth cycle. KDU731 displayed the most promising profile, with low nanomolar (102 nM ± 2.28) activity and negligible host cell toxicity. This study offers new insights into the relative efficacy and safety of various anti-cryptosporidial compounds, highlighting their stage-specific effects on and the consequential impacts on host cells. Identifying safe and effective anti-cryptosporidial agents contributes significantly to the One Health approach, which emphasizes the importance of integrated strategies in controlling zoonotic diseases.
本研究评估了抗隐孢子虫药物硝唑尼特、常山酮、吡唑并吡啶类似物KDU731和巴龙霉素（PMC）对抗重要人畜共患病原体的有效性。该研究利用HCT - 8宿主细胞进行培养，并采用荧光显微镜/定量聚合酶链反应（qPCR）检测寄生虫生长情况。通过计算化合物在感染后48小时对寄生虫总生长的抑制浓度（IC）来评估其疗效。该研究进一步考察了这些化合物对早期寄生泡（PV）形成、裂殖子逸出、宿主细胞活力和细胞生长周期的影响。KDU731表现出最有前景的特性，具有低纳摩尔（102 nM ± 2.28）活性且对宿主细胞毒性可忽略不计。本研究为各种抗隐孢子虫化合物的相对疗效和安全性提供了新见解，突出了它们对寄生虫的阶段特异性作用以及对宿主细胞的相应影响。确定安全有效的抗隐孢子虫药物对“同一个健康”方法有重大贡献，该方法强调综合策略在控制人畜共患病中的重要性。
