Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase.
Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase.
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DOI：
10.1073/pnas.96.23.13387
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发表时间：
1999-11
影响因子：
11.1
通讯作者：
E. Zuther;Jennifer J. Johnson;R. Haselkorn;R. McLeod;P. Gornicki
中科院分区：
文献类型：
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作者：
E. Zuther;Jennifer J. Johnson;R. Haselkorn;R. McLeod;P. Gornicki
草质体乙酰辅酶A羧化酶（ACC）抑制剂芳氧苯氧丙酸酯也能抑制弓形虫ACC。人成纤维细胞中的弓形虫在10 μ M下2天内减少70%，并且在10 - 100 μ M下2 - 4天内有效地消除寄生虫。即使在高得多的浓度下，Clodinafop对宿主细胞也没有毒性。不同除草剂对寄生虫生长的抑制与其抑制ACC酶活性的能力相关，表明ACC是这些药剂的靶标。编码T.对弓形虫、恶性疟原虫、诺氏疟原虫和微小隐孢子虫进行了测序。一个T结果表明，弓形虫ACC（ACC 1）的氨基酸序列与恶性疟原虫ACC、诺氏疟原虫ACC和隐小环藻（Cyclotella cryptica）叶绿体ACC聚在一起，另一序列（ACC 2）与隐小环藻（C. parvum ACC，可能是胞质形式。
Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 microM in 2 days and effectively eliminates the parasite in 2-4 days at 10-100 microM. Clodinafop is not toxic to the host cell even at much higher concentrations. Parasite growth inhibition by different herbicides is correlated with their ability to inhibit ACC enzyme activity, suggesting that ACC is a target for these agents. Fragments of genes encoding the biotin carboxylase domain of multidomain ACCs of T. gondii, Plasmodium falciparum, Plasmodium knowlesi, and Cryptosporidium parvum were sequenced. One T. gondii ACC (ACC1) amino acid sequence clusters with P. falciparum ACC, P. knowlesi ACC, and the putative Cyclotella cryptica chloroplast ACC. Another sequence (ACC2) clusters with that of C. parvum ACC, probably the cytosolic form.