A novel fungal metabolite inhibits Plasmodium falciparum transmission and infection.
A novel fungal metabolite inhibits Plasmodium falciparum transmission and infection.
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一种新的真菌代谢产物抑制恶性疟原虫传播和感染。
DOI：
10.1186/s13071-021-04677-7
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发表时间：
2021-03-24
影响因子：
3.2
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Niu G;Wang X;Hao Y;Kandel S;Niu G;Raptis RG;Li J
疟疾的传播依赖于受感染的蚊子，可以通过阻断传播的药物加以控制。最近发现的FREP 1介导的疟疾传播途径是筛选限制传播药物的绝佳目标。为了鉴定候选小分子，我们使用基于ELISA的方法来分析来自真菌文库的提取物以抑制FREP 1-寄生虫相互作用。通过色谱法和晶体学方法分别分离和鉴定了一个活性化合物。我们通过标准的膜喂养试验（SMFA）和通过培养对血液中寄生虫增殖的生物活性化合物对疟疾传播到蚊子的影响进行了测量。我们发现淡紫紫孢菌的乙酸乙酯提取物可以抑制恶性疟原虫向蚊子的传播。预先暴露于提取物使冈比亚按蚊对疟原虫感染具有抵抗力。此外，我们从提取物中分离出一种新的活性化合物，并将其鉴定为3-氨基-7，9-二羟基-1-甲基-6H-苯并[c]色烯-6-酮或“普利辛”。Pulixin阻止FREP 1与恶性疟原虫感染的细胞裂解物结合。Pulixin阻断了寄生虫向蚊子的传播，基于SMFA的EC 50（产生半数最大反应的浓度）为11 µM。值得注意的是，普利辛还可以抑制无性繁殖期恶性疟原虫的增殖，EC 50为47 nM。该化合物在116 µM或更低浓度下未显示出细胞毒性作用。通过靶向FREP 1-疟原虫相互作用，我们发现淡紫紫孢菌提取物阻断了疟疾传播。我们分离并鉴定了生物活性剂普利新作为一种新的化合物，能够阻止疟疾传播给蚊子，并抑制血培养中寄生虫的增殖。在线版本包含补充材料，可通过10.1186/s13071-021-04677-7获得。
Malaria transmission depends on infected mosquitoes and can be controlled by transmission-blocking drugs. The recently discovered FREP1-mediated malaria transmission pathway is an excellent target to screen drugs for limiting transmission. To identify candidate small molecules, we used an ELISA-based approach to analyze extracts from a fungal library for inhibition of the FREP1–parasite interaction. We isolated and determined one active compound by chromatography and crystallography, respectively. We measured the effects of the bioactive compound on malaria transmission to mosquitoes through standard membrane-feeding assays (SMFA) and on parasite proliferation in blood by culturing. We discovered the ethyl acetate extract of the fungus Purpureocillium lilacinum that inhibited Plasmodium falciparum transmission to mosquitoes. Pre-exposure to the extract rendered Anopheles gambiae resistant to Plasmodium infection. Furthermore, we isolated one novel active compound from the extract and identified it as 3-amino-7,9-dihydroxy-1-methyl-6H-benzo[c]chromen-6-one, or “pulixin.” Pulixin prevented FREP1 from binding to P. falciparum-infected cell lysate. Pulixin blocked the transmission of the parasite to mosquitoes with an EC50 (the concentration that gave half-maximal response) of 11 µM based on SMFA. Notably, pulixin also inhibited the proliferation of asexual-stage P. falciparum with an EC50 of 47 nM. The compound did not show cytotoxic effects at a concentration of 116 µM or lower. By targeting the FREP1–Plasmodium interaction, we discovered that Purpureocillium lilacinum extract blocked malaria transmission. We isolated and identified the bioactive agent pulixin as a new compound capable of stopping malaria transmission to mosquitoes and inhibiting parasite proliferation in blood culture. The online version contains supplementary material available at 10.1186/s13071-021-04677-7.
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影响因子：
4.6
作者：
Niu, Guodong;Hao, Yue;Li, Jun
通讯作者：
Li, Jun
DOI：
10.1093/bioinformatics/btw108
发表时间：
2016-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Katoh K;Standley DM
通讯作者：
Standley DM
影响因子：
3.7
作者：
Rahbari, Mahsa;Rahlfs, Stefan;Becker, Katja
通讯作者：
Becker, Katja
影响因子：
4.6
作者：
Niu G;Wang B;Zhang G;King JB;Cichewicz RH;Li J
通讯作者：
Li J
DOI：
10.1073/pnas.1321024110
发表时间：
2013-12-17
影响因子：
11.1
作者：
Li, Jun;Wang, Xiaohong;James, Anthony A.
通讯作者：
James, Anthony A.