Hydroxylamine and Carboxymethoxylamine Can Inhibit Toxoplasma gondii Growth through an Aspartate Aminotransferase-Independent Pathway

文献类型： 外文期刊

第一作者： Li, Jixu

作者： Li, Jixu;Guo, Huanping;Galon, Eloiza May;Gao, Yang;Lee, Seung-Hun;Liu, Mingming;Li, Yongchang;Ji, Shengwei;Xuan, Xuenan;Lee, Seung-Hun;Jia, Honglin

作者机构：

关键词： Toxoplasma gondii; toxoplasmosis; hydroxylamine; carboxymethoxylamine; aspartate aminotransferase

期刊名称：ANTIMICROBIAL AGENTS AND CHEMOTHERAPY （ 影响因子：5.191； 五年影响因子：5.346 ）

ISSN： 0066-4804

年卷期： 2020 年 64 卷 3 期

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收录情况： SCI

摘要： Toxoplasma gondii is an obligate intracellular protozoan parasite and a successful parasitic pathogen in diverse organisms and host cell types. Hydroxylamine (HYD) and carboxymethoxylamine (CAR) have been reported as inhibitors of aspartate aminotransferases (AATs) and interfere with the proliferation in Plasmodium falciparum. Therefore, AATs are suggested as drug targets against Plasmodium. The T. gondii genome encodes only one predicted AAT in both T. gondii type I strain RH and type II strain PLK. However, the effects of HYD and CAR, as well as their relationship with AAT, on T. gondii remain unclear. In this study, we found that HYD and CAR impaired the lytic cycle of T. gondii in vitro, including the inhibition of invasion or reinvasion, intracellular replication, and egress. Importantly, HYD and CAR could control acute toxoplasmosis in vivo. Further studies showed that HYD and CAR could inhibit the transamination activity of rTgAAT in vitro. However, our results confirmed that deficiency of AAT in both RH and PLK did not reduce the virulence in mice, although the growth ability of the parasites was affected in vitro. HYD and CAR could still inhibit the growth of AAT-deficient parasites. These findings indicated that HYD and CAR inhibition of T. gondii growth and control of toxoplasmosis can occur in an AAT-independent pathway. Overall, further studies focusing on the elucidation of the mechanism of inhibition are warranted. Our study hints at new substrates of HYD and CAR as potential drug targets to inhibit T. gondii growth.

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