The antifungal Aureobasidin A and an analogue are active against the protozoan parasite Toxoplasma gondii but do not inhibit sphingolipid biosynthesis - Corrigendum.
The antifungal Aureobasidin A and an analogue are active against the protozoan parasite Toxoplasma gondii but do not inhibit sphingolipid biosynthesis - Corrigendum.
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DOI：
10.1017/s0031182017000877
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发表时间：
2018-03
期刊：
影响因子：
2.4
通讯作者：
Denny PW
中科院分区：
文献类型：
--
作者：
Alqaisi AQI;Mbekeani AJ;Llorens MB;Elhammer AP;Denny PW
弓形虫是尖端复合门的一种专性胞内原生动物寄生虫，弓形虫病是人类和重要经济动物的重要疾病。由于可用的药物种类有限，有必要确定新的治疗化合物。金黄色葡萄糖素A(ABA)是一种针对病原真菌中必需的肌醇磷脂(IPC)合成酶的抗真菌药物。这种天然的环状去脂肽也抑制弓形虫的繁殖，原生动物IPC合成酶同源物被认为是靶点。这里提供的数据表明，ABA和类似物(化合物20)都不针对原生动物IPC合成酶同源物或总寄生虫鞘脂合成。然而，进一步的分析证实，ABA对弓形虫的增殖型速殖子具有显著的活性，而化合物20虽然有效，但效果较差。在分析这些化合物对分离的弓形虫的直接作用时，这种差异更加明显，表明ABA具有快速杀菌作用。重要的是，证明了用ABA和化合物20靶向包囊、缓速殖子形式的寄生虫的可能性，表明这类化合物可能为第一次有效治疗慢性弓形虫病提供基础。
Toxoplasma gondii is an obligate intracellular protozoan parasite of the phylum Apicomplexa, and toxoplasmosis is an important disease of both humans and economically important animals. With a limited array of drugs available there is a need to identify new therapeutic compounds. Aureobasidin A (AbA) is an antifungal that targets the essential inositol phosphorylceramide (IPC, sphingolipid) synthase in pathogenic fungi. This natural cyclic depsipeptide also inhibits Toxoplasma proliforation, with the protozoan IPC synthase orthologue proposed as the target. The data presented here show that neither AbA nor an analogue (Compound 20), target the protozoan IPC synthase orthologue or total parasite sphingolipid synthesis. However, further analyses confirm that AbA exhibits significant activity against the proliferative tachyzoite form of Toxoplasma, and Compound 20, whilst effective, has reduced efficacy. This difference was more evident on analyses of the direct effect of these compounds against isolated Toxoplasma, indicating that AbA is rapidly microbicidal. Importantly, the possibility of targeting the encysted, bradyzoite, form of the parasite with AbA and Compound 20 was demonstrated, indicating that this class of compounds may provide the basis for the first effective treatment for chronic toxoplasmosis.