Key Laboratory of Prevention and Control for Animal Disease, College of Animal Science & Technology, Guangxi University, Nanning 530004, China.
Int J Mol Sci. 2022 Aug 24;23(17):9586. doi: 10.3390/ijms23179586.
is a widespread intracellular pathogen that infects humans and a variety of animals. The current therapeutic strategy for human toxoplasmosis is a combination of sulphadiazine and pyrimethamine. However, this combination still has a high failure rate and is ineffective against chronic infections. Therefore, it is important to discover a new anti- drug that is safer and more effective in both humans and animals. In this study, we describe the anti- activities of the 16-membered macrolide tilmicosin and acetylisovaleryltylosin tartrate (ATLL). Both tilmicosin and ATLL potently inhibited with a half-maximal effective concentration (EC) of 17.96 μM and 10.67 μM, respectively. Interestingly, tilmicosin and ATLL had different effects on the parasites. ATLL exhibited a potent inhibitory effect on intracellular parasite growth, while tilmicosin suppressed parasites extracellularly. By studying the lytic cycle of after treatment, we found that ATLL potently inhibited the intracellular proliferation of tachyzoites, while tilmicosin affected the invasion of tachyzoites. Immunofluorescence analysis using ATLL-treated showed morphologically abnormal parasites, which may be due to the inhibition of tachyzoite proliferation and division. In addition, tilmicosin and ATLL significantly delayed the death of mice caused by acute toxoplasmosis. Our results suggest that ATLL has potent anti- activity both in vitro and in vivo and may be an alternative to toxoplasmosis in the future.
弓形虫是一种广泛存在于细胞内的病原体，可感染人类和多种动物。目前，人类弓形虫病的治疗策略是磺胺嘧啶和乙胺嘧啶的联合用药。然而，这种联合用药仍然存在很高的失败率，并且对慢性感染无效。因此，发现一种新的抗弓形虫药物，在人类和动物中更安全、更有效是非常重要的。在本研究中，我们描述了 16 元大环内酯类药物替米考星和乙酰异戊酰泰乐菌素（ATLL）的抗弓形虫活性。替米考星和 ATLL 均能有效抑制弓形虫，半数有效浓度（EC）分别为 17.96 μM 和 10.67 μM。有趣的是，替米考星和 ATLL 对寄生虫的作用方式不同。ATLL 对细胞内寄生虫生长表现出强大的抑制作用，而替米考星则抑制寄生虫的胞外生长。通过研究处理后弓形虫的裂解周期，我们发现 ATLL 能强烈抑制速殖子的胞内增殖，而替米考星则影响速殖子的入侵。用 ATLL 处理的弓形虫进行免疫荧光分析显示，形态异常的寄生虫，这可能是由于速殖子增殖和分裂受到抑制。此外，替米考星和 ATLL 显著延缓了急性弓形虫病小鼠的死亡。我们的研究结果表明，ATLL 在体外和体内均具有强大的抗弓形虫活性，可能成为未来弓形虫病的替代药物。
