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果蝇抗菌肽Mtk-1和Mtk-2对疟原虫恶性疟原虫具有活性。

The Drosophila melanogaster antimicrobial peptides Mtk-1 and Mtk-2 are active against the malarial parasite Plasmodium falciparum.

作者信息

Tonk Miray, Pierrot Christine, Cabezas-Cruz Alejandro, Rahnamaeian Mohammad, Khalife Jamal, Vilcinskas Andreas

机构信息

LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325, Frankfurt, Germany.

Institute for Insect Biotechnology, Justus Liebig University of Giessen, Heinrich-Buff-Ring 26-32, 35392, Giessen, Germany.

出版信息

Parasitol Res. 2019 Jun;118(6):1993-1998. doi: 10.1007/s00436-019-06305-x. Epub 2019 Apr 18.

Abstract

Antimicrobial peptides (AMPs) are important components of the vertebrate and invertebrate innate immune systems. Although AMPs are widely recognized for their broad-spectrum activity against bacteria, fungi, and viruses, their activity against protozoan parasites has not been investigated in detail. In this study, we tested 10 AMPs from three different insect species: the greater wax moth Galleria mellonella (cecropin A-D), the fruit fly Drosophila melanogaster (drosocin, Mtk-1 and Mtk-2), and the blow fly Lucilia sericata (LSerPRP-2, LSerPRP-3 and stomoxyn). We tested each AMP against the protozoan parasite Plasmodium falciparum which is responsible for the most severe form of malaria in humans. We also evaluated the impact of these insect AMPs on mouse and pig erythrocytes. Whereas all AMPs showed low hemolytic effects towards mouse and pig erythrocytes, only D. melanogaster Mtk-1 and Mtk-2 significantly inhibited the growth of P. falciparum at low concentrations. Mtk-1 and Mtk-2 could therefore be considered as leads for the development of antiparasitic drugs targeting the clinically important asexual blood stage of P. falciparum.

摘要

抗菌肽(AMPs)是脊椎动物和无脊椎动物先天免疫系统的重要组成部分。尽管抗菌肽因其对细菌、真菌和病毒的广谱活性而被广泛认可,但其对原生动物寄生虫的活性尚未得到详细研究。在本研究中,我们测试了来自三种不同昆虫物种的10种抗菌肽:大蜡螟(Galleria mellonella)(天蚕素A-D)、果蝇(Drosophila melanogaster)(果蝇抗菌肽、Mtk-1和Mtk-2)以及丝光绿蝇(Lucilia sericata)(LSerPRP-2、LSerPRP-3和厩螫蝇素)。我们测试了每种抗菌肽对导致人类最严重疟疾形式的原生动物寄生虫恶性疟原虫(Plasmodium falciparum)的作用。我们还评估了这些昆虫抗菌肽对小鼠和猪红细胞的影响。尽管所有抗菌肽对小鼠和猪红细胞均显示出低溶血作用,但只有果蝇的Mtk-1和Mtk-2在低浓度下能显著抑制恶性疟原虫的生长。因此,Mtk-1和Mtk-2可被视为开发针对恶性疟原虫临床上重要的无性血液阶段的抗寄生虫药物的先导物。

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