Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI, 53706, USA.
Parasitol Res. 2013 Nov;112(11):3859-63. doi: 10.1007/s00436-013-3574-1. Epub 2013 Aug 16.
Fusidic acid is a bacteriostatic antibiotic that inhibits the growth of bacteria by preventing the release of translation elongation factor G (EF-G) from the ribosome. The apicomplexan parasite Toxoplasma gondii has an orthologue of bacterial EF-G that can complement bacteria and is necessary for parasite virulence. Fusidic acid has been shown to be effective in tissue culture against the related pathogen Plasmodium falciparum, and current drug treatments against T. gondii are limited. We therefore investigated the therapeutic value of fusidic acid for T. gondii and found that the drug was effective in tissue culture, but not in a mouse model of infection. To determine whether this trend would occur in another intracellular pathogen that elicits a T helper 1-type immune response, we tested the efficacy of fusidic acid for the bacterium Listeria monocytogenes. Similar to its effects on T. gondii, fusidic acid inhibits the growth of L. monocytogenes in vitro, but not in mice. These findings highlight the necessity of in vivo follow-up studies to validate in vitro drug investigations.
夫西地酸是一种抑菌抗生素，通过阻止翻译延伸因子 G（EF-G）从核糖体释放来抑制细菌生长。顶复门寄生虫刚地弓形虫有一种细菌 EF-G 的同源物，它可以补充细菌，并且是寄生虫毒力所必需的。夫西地酸已被证明在组织培养中对相关病原体疟原虫有效，而目前针对刚地弓形虫的药物治疗有限。因此，我们研究了夫西地酸对刚地弓形虫的治疗价值，发现该药物在组织培养中有效，但在感染的小鼠模型中无效。为了确定这种趋势是否会发生在另一种引发 Th1 型免疫反应的细胞内病原体中，我们测试了夫西地酸对李斯特菌的疗效。与对刚地弓形虫的作用相似，夫西地酸抑制李斯特菌在体外的生长，但在小鼠体内无效。这些发现强调了进行体内后续研究以验证体外药物研究的必要性。
