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

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.

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Acknowledgments

We thank Dr. Richard M. Twyman for editing the manuscript, Dr. Irina Häcker for providing pig blood, and Sophia Lafitte for technical assistance.

Funding

The authors would like to acknowledge generous funding by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK) via the LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG) and the LOEWE Center for Insect Biotechnology and Bioresources.

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Correspondence to Miray Tonk.

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Supplementary Figure 1

Representative illustration of flow cytometry analysis ofPlasmodiumgrowth inhibition. Non infected (A) or P. falciparum-infected human erythrocytes (B, C) were incubated with vehicle (B) or with 50 μM Mtk-1 AMP (C) for 48 h at 37 °C. Red blood cells were gated according to their FSC-SSC parameters (dot plots, left panels, P2) and parasites were detected among them as SybrGreen-positive cells (histograms, right panels, P3). Total red blood cells (P2) represent 94.4%, 90.4% and 92.5% of total events for non-infected negative control (A), infected positive control (B) and Mtk-1-treated parasites (C) respectively. SybrGreen-positive cells detected in (A) correspond to staining background. (JPG 108 kb)

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Tonk, M., Pierrot, C., Cabezas-Cruz, A. et al. The Drosophila melanogaster antimicrobial peptides Mtk-1 and Mtk-2 are active against the malarial parasite Plasmodium falciparum. Parasitol Res 118, 1993–1998 (2019). https://doi.org/10.1007/s00436-019-06305-x

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Keywords

  • Insect antimicrobial peptides
  • Metchnikowin
  • Drosophila melanogaster
  • Galleria mellonella
  • Lucilia sericata