Inhibitory Effects of Fosmidomycin Against Babesia microti in vitro
Inhibitory Effects of Fosmidomycin Against Babesia microti in vitro
复制标题
磷米霉素对田鼠巴贝斯虫的体外抑制作用
DOI：
10.3389/fcell.2020.00247
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发表时间：
2020-04
影响因子：
5.5
通讯作者：
He Lan
中科院分区：
文献类型：
--
作者：
Wang Sen;Li Muxiao;Luo Xiaoying;Yu Long;Nie Zheng;Liu Qin;An Xiaomeng;Ao Yangsiqi;Chen Jiaxu;Tian Yu;Zhao Junlong;He Lan
巴贝斯虫是引起人类巴贝斯虫病的主要病原体，已有报道巴贝斯虫对阿奇霉素+阿托伐醌和克林霉素+奎宁的传统治疗方法表现出耐药性，提示开发新药的必要性。甲基-β-4-磷酸（MEP）途径是顶复门寄生虫特有的一条途径，在恶性疟原虫的生长过程中起着至关重要的作用。在MEP途径中，1-脱氧-D-木酮糖5-磷酸还原异构酶（DXR）是一种限速酶，磷霉素（FSM）是该酶的抑制剂。DXR已显示为抗疟药物靶点，但关于B尚无报道。Microti DXR（BmDXR）。本研究对BmDXR基因进行了克隆、测序和生物信息学分析，并将其作为抑制B生长的潜在药物靶点进行了评价。micorti in vitro.通过在B中加入不同浓度的FSM进行药物测定。试管培养通过在培养基中添加200 μM异戊烯焦磷酸盐（IPP）或5 μM香叶基香叶醇（GG-ol）以及5 μM FSM或10 μM乙酰氨基二氮烯（diminazene aceturate）进行拯救实验。结果表明，FSM对B的生长有抑制作用。在体外培养中，IPP和GG-ol均能恢复田鼠的生长，IC_（50）为4.63 ± 0.12 μM。此外，FSM显示通过抑制DXR活性来抑制寄生虫的生长，这与其他顶复门寄生虫的报道结果一致。我们的研究结果表明DXR作为控制B的药物靶点的潜力。而FSM对B的生长有抑制作用。离体培养的Microti。
Babesia microti, the main pathogen causing human babesiosis, has been reported to exhibit resistance to the traditional treatment of azithromycin + atovaquone and clindamycin + quinine, suggesting the necessity of developing new drugs. The methylerythritol 4-phosphate (MEP) pathway, a unique pathway in apicomplexan parasites, was shown to play a crucial function in the growth of Plasmodium falciparum. In the MEP pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is a rate-limiting enzyme and fosmidomycin (FSM) is a reported inhibitor for this enzyme. DXR has been shown as an antimalarial drug target, but no report is available on B. microti DXR (BmDXR). Here BmDXR was cloned, sequenced, analyzed by bioinformatics, and evaluated as a potential drug target for inhibiting the growth of B. micorti in vitro. Drug assay was performed by adding different concentrations of FSM in B. microti in vitro culture. Rescue experiment was done by supplementing 200 μM isopentenyl pyrophosphate (IPP) or 5 μM geranylgeraniol (GG-ol) in the culture medium together with 5 μM FSM or 10 μM diminazene aceturate. The results indicated that FSM can inhibit the growth of B. microti in in vitro culture with an IC50 of 4.63 ± 0.12 μM, and growth can be restored by both IPP and GG-ol. Additionally, FSM is shown to inhibit the growth of parasites by suppressing the DXR activity, which agreed with the reported results of other apicomplexan parasites. Our results suggest the potential of DXR as a drug target for controlling B. microti and that FSM can inhibit the growth of B. microti in vitro.
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DOI：
10.1016/0035-9203(83)90129-3
发表时间：
1983
影响因子：
2.2
作者：
Z. L. Li;H. Gu;D. Warhurst;W. Peters
通讯作者：
Z. L. Li;H. Gu;D. Warhurst;W. Peters
影响因子：
4.6
作者：
Umeda, Tomonobu;Tanaka, Nobutada;Kusakabe, Yoshio;Nakanishi, Masayuki;Kitade, Yukio;Nakamura, Kazuo T.
通讯作者：
Nakamura, Kazuo T.
影响因子：
3.4
作者：
Wiback, SJ;Palsson, BO
通讯作者：
Palsson, BO
影响因子：
1.3
作者：
RUEBUSH, MJ;HANSON, WL
通讯作者：
HANSON, WL
影响因子：
5.2
作者：
Imlay, Leah;Odom, Audrey R
通讯作者：
Odom, Audrey R