Design and Activity of Antimicrobial Peptides against Sporogonic-Stage Parasites Causing Murine Malarias

Abstract

Insects produce several types of peptides to combat a broad spectrum of invasive pathogenic microbes, including protozoans. However, despite this defense response, infections are often established. Our aim was to design novel peptides that produce high rates of mortality among protozoa of the genus Plasmodium, the malaria parasites. Using existing antimicrobial peptide sequences as templates, we designed and synthesized three short novel hybrids, designated Vida1 to Vida3. Each has a slightly different predicted secondary structure. The peptides were tested against sporogonic stages of the rodent malaria parasites Plasmodium berghei (in vitro and in vivo) and P. yoelii nigeriensis (in vitro). The level of activity varied for each peptide and according to the parasite stage targeted. Vida3 (which is predicted to have large numbers of ␤ sheets and coils but no ␣ helices) showed the highest level of activity, killing the early sporogonic stages in culture and causing highly significant reductions in the prevalence and intensity of infection of P. berghei after oral administration or injection in Anopheles gambiae mosquitoes. The secondary structures of these peptides may play a crucial role in their ability to interact with and kill sporogonic forms of the malaria parasite.

The Antimicrobial Peptide NK-2, the Core Region of Mammalian NK-Lysin, Kills Intraerythrocytic Plasmodium falciparum

“…The recently reported idea that antimicrobial peptides, fusogenic peptides, and cell-penetrating peptides may better be unified as "membrane active peptides" makes the enormous variety of presumably interesting templates for potentially biomedically valuable peptides even clearer (21). However, only a very limited number of antimicrobial peptides are known to be effective against eukaryotic pathogens (5,19,42,44).…”

Effect of the antimicrobial peptide gomesin against different life stages of Plasmodium spp.

“…Vida 1-3, P2WN, ILF, SM1, SB-37, and Shiva-1 and 3 (Jaynes et al, 1988;Rodriguez et al, 1995;Possani et al, 1998;Ghosh et al, 2001;Arrighi et al, 2002). These peptides have a broad spectrum of action and permeate cell membranes by incompletely understood mechanisms.…”

Beyond Lysozyme: Antimicrobial Peptides Against Malaria

“…For instance, Arrighi and colleagues designed new AMPs starting from natural or synthetic antimicrobial polypeptides and observed that peptides with no particular secondary structures (containing mainly random coils and turns) were more active on the sporogonic stages of P. berghei and P. yoelii (Arrighi et al 2002).…”