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- Title
In Vitro and In Vivo Activities of Tilmicosin and Acetylisovaleryltylosin Tartrate against Toxoplasma gondii.
- Authors
Ma, Yazhen; Cao, Xinru; Wang, Hui; Song, Xingju; Hu, Dandan
- Abstract
Toxoplasma gondii 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-T. gondii drug that is safer and more effective in both humans and animals. In this study, we describe the anti-T. gondii activities of the 16-membered macrolide tilmicosin and acetylisovaleryltylosin tartrate (ATLL). Both tilmicosin and ATLL potently inhibited T. gondii with a half-maximal effective concentration (EC50) 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 T. gondii 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 T. gondii 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-Toxoplasma activity both in vitro and in vivo and may be an alternative to toxoplasmosis in the future.
- Subjects
TOXOPLASMA gondii; LYTIC cycle; TOXOPLASMOSIS; INTRACELLULAR pathogens; SULFADIAZINE; IMMUNOFLUORESCENCE
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 17, p9586
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23179586