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.
KeywordsInsect antimicrobial peptides Metchnikowin Drosophila melanogaster Galleria mellonella Lucilia sericata
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 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 8:201–209Google Scholar
- 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 1:939–945Google Scholar
- 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 15:14893–14897Google Scholar
- 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 11:80CrossRefGoogle Scholar
- 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 233:694–700Google Scholar
- Mak P, Chmiel D, Gacek GJ (2001) Antibacterial peptides of the moth Galleria mellonella. Acta Biochim Pol 48:1191–1195Google Scholar
- 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 284:119–133CrossRefGoogle Scholar
- 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 59:2508–2514Google Scholar
- Pretzel J, Mohring F, Rahlfs S, Becker K (2013) Antiparasitic peptides. Adv Biochem Eng Biotechnol 135:157–192Google Scholar
- World Health Organization (2018) Malaria fact sheet. Available at http://www.who.int/en/news-room/fact-sheets/detail/malaria Accessed 29 Nov 2018