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


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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  1. Bechinger B (2004) Structure and function of membrane-lytic peptides. Crit Rev Plant Sci 23(3):271–292

    CAS  Article  Google Scholar 

  2. Bencivengo AM, Cudic M, Hoffmann R, Otvos L (2001) The efficacy of the antibacterial peptide, pyrrhocoricin, is finely regulated by its amino acid residues and active domains. LIPS 8:201–209

    CAS  Google Scholar 

  3. Bolouri Moghaddam MR, Tonk M, Schreiber C, Salzig D, Czermak P, Vilcinskas A, Rahnamaeian M (2016) The potential of the Galleria mellonella innate immune system is maximized by the co-presentation of diverse antimicrobial peptides. Biol Chem 1:939–945

    CAS  Article  Google Scholar 

  4. Bolouri Moghaddam MR, Vilcinskas A, Rahnamaeian M (2017a) The insect-derived antimicrobial peptide metchnikowin targets Fusarium graminearum β(1,3) glucanosyltransferase Gel1, which is required for the maintenance of cell wall integrity. Biol Chem 398:491–498

    CAS  Article  Google Scholar 

  5. Bolouri Moghaddam MR, Gross T, Becker A, Vilcinskas A, Rahnamaeian M (2017b) The selective antifungal activity of Drosophila melanogaster metchnikowin reflects the species-dependent inhibition of succinate-coenzyme Q reductase. Sci Rep 7(1):8192

    Article  Google Scholar 

  6. Bulet P, Dimarcq JL, Hetru C, Lagueux M, Charlet M, Hegy G, Van Dorsselaer A, Hoffmann JA (1993) A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution. J Biol Chem 15:14893–14897

  7. El Chamy Maluf S, Dal Mas C, Oliveira E, Melo P, Carmona A, Gazarini M, Hayashi M (2016) Inhibition of malaria parasite Plasmodium falciparum development by crotamine, a cell penetrating peptide from the snake venom. Peptides 78:11–16

    Article  Google Scholar 

  8. Fréville A, Cailliau-Maggio K, Pierrot C, Tellier G, Kalamou G, Lafitte S, Martoriati A, Pierce RJ, Bodart JF, Khalife J (2013) Plasmodium falciparum encodes a conserved active inhibitor-2 for protein phosphatase type 1: perspectives for novel anti-plasmodial therapy. BMC Biol 11:80

    Article  Google Scholar 

  9. Hemingway J, Shretta R, Wells TN, Bell D, Djimdé AA, Achee N, Qi G (2016) Tools and strategies for malaria control and elimination: what do we need to achieve a grand convergence in malaria? PLoS Biol 14:e1002380

    Article  Google Scholar 

  10. Izumiyama S, Omura M, Takasaki T, Ohmae H, Asahi H (2009) Plasmodium falciparum: development and validation of a measure of intraerythrocytic growth using SYBR Green I in a flow cytometer. Exp Parasitol 121:144–150

    CAS  Article  Google Scholar 

  11. Levashina EA, Ohresser S, Bulet P, Reichhart JM, Hetru C, Hoffmann JA (1995) Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties. FEBS J 233:694–700

    CAS  Google Scholar 

  12. Mak P, Chmiel D, Gacek GJ (2001) Antibacterial peptides of the moth Galleria mellonella. Acta Biochim Pol 48:1191–1195

  13. Mason AJ, Moussaoui W, Abdelrahman T, Boukhari A, Bertani P, Marquette A, Shooshtarizaheh P, Moulay G, Boehm N, Guerold B (2009) Structural determinants of antimicrobial and antiplasmodial activity and selectivity in histidine-rich amphipathic cationic peptides. J Biol Chem 284:119–133

    CAS  Article  Google Scholar 

  14. Mylonakis E, Podsiadlowski L, Muhammed M, Vilcinskas A (2016) Diversity, evolution and medical applications of insect antimicrobial peptides. Phil Trans R Soc Lond B Biol Sci 371:20150290

    Article  Google Scholar 

  15. Pöppel AK, Vogel H, Wiesner J, Vilcinskas A (2015) Antimicrobial peptides expressed in medicinal maggots of the blow fly Lucilia sericata show combinatorial activity against bacteria. Antimicrob Agents Chemother 59:2508–2514

    Article  Google Scholar 

  16. Pretzel J, Mohring F, Rahlfs S, Becker K (2013) Antiparasitic peptides. Adv Biochem Eng Biotechnol 135:157–192

    CAS  PubMed  Google Scholar 

  17. Rahnamaeian M, Vilcinskas A (2012) Defense gene expression is potentiated in transgenic barley expressing antifungal peptide metchnikowin throughout powdery mildew challenge. J Plant Res 125:115–124

    CAS  Article  Google Scholar 

  18. Rahnamaeian M, Langen G, Imani J, Khalifa W, Altincicek B, von Wettstein D, Kogel KH, Vilcinskas A (2009) Insect peptide metchnikowin confers on barley a selective capacity for resistance to ascomycetes fungal pathogens. J Exp Bot 60:4105–4114

    CAS  Article  Google Scholar 

  19. Rahnamaeian M, Cytryńska M, Zdybicka-Barabas A, Vilcinskas A (2016) The functional interaction between abaecin and pore-forming peptides indicates a general mechanism of antibacterial potentiation. Peptides 78:17–23

    CAS  Article  Google Scholar 

  20. Rodriguez M, Zamudio F, Torres JA, Gonzalezceron L, Possani LD, Rodriguez MH (1995) Effect of a cecropin-like synthetic peptide (Shiva-3) on the sporogonic development of Plasmodium berghei. Exp Parasitol 80:596–604

    CAS  Article  Google Scholar 

  21. Shahabuddin M, Fields I, Bulet P, Hoffmann JA, Miller LH (1998) Plasmodium gallinaceum: differential killing of some mosquito stages of the parasite by insect defensin. Exp Parasitol 89:103–112

    CAS  Article  Google Scholar 

  22. Tonk M, Vilcinskas A (2017) The medical potential of antimicrobial peptides from insects. Curr Top Med Chem 17:554–575

    CAS  Article  Google Scholar 

  23. World Health Organization (2018) Malaria fact sheet. Available at Accessed 29 Nov 2018

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


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).

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