Killer Bee Molecules: Antimicrobial Peptides as Effector Molecules to Target Sporogonic Stages of Plasmodium

Abstract

A new generation of strategies is evolving that aim to block malaria transmission by employing genetically modified vectors or mosquito pathogens or symbionts that express anti-parasite molecules. Whilst transgenic technologies have advanced rapidly, there is still a paucity of effector molecules with potent anti-malaria activity whose expression does not cause detrimental effects on mosquito fitness. Our objective was to examine a wide range of antimicrobial peptides (AMPs) for their toxic effects on Plasmodium and anopheline mosquitoes. Specifically targeting early sporogonic stages, we initially screened AMPs for toxicity against a mosquito cell line and P. berghei ookinetes. Promising candidate AMPs were fed to mosquitoes to monitor adverse fitness effects, and their efficacy in blocking rodent malaria infection in Anopheles stephensi was assessed. This was followed by tests to determine their activity against P. falciparum in An. gambiae, initially using laboratory cultures to infect mosquitoes, then culminating in preliminary assays in the field using gametocytes and mosquitoes collected from the same area in Mali, West Africa. From a range of 33 molecules, six AMPs able to block Plasmodium development were identified: Anoplin, Duramycin, Mastoparan X, Melittin, TP10 and Vida3. With the exception of Anoplin and Mastoparan X, these AMPs were also toxic to an An. gambiae cell line at a concentration of 25 µM. However, when tested in mosquito blood feeds, they did not reduce mosquito longevity or egg production at concentrations of 50 µM. Peptides effective against cultured ookinetes were less effective when tested in vivo and differences in efficacy against P. berghei and P. falciparum were seen. From the range of molecules tested, the majority of effective AMPs were derived from bee/wasp venoms.

Beyond Lysozyme: Antimicrobial Peptides Against Malaria

“…A recent work by Carter and colleagues investigated the effect of 33 AMPs on Plasmodium early sporogonic stages, verifying that they did not alter mosquitoes' fitness (Carter et al 2013). Table 7.2 summarizes the antiplasmodial activity of some AMPs.…”

“…The majority of AMPs with antimalarial activity described by Carter and colleagues were derived from bee/wasp venoms (Carter et al 2013).…”

Antimicrobial peptides: a new class of antimalarial drugs?

“…The mortality rate of: Vida1 was 65% on young ookinetes (10 h), Vida2 was 60–70% on maturing ookinetes (14 and 24 h), and Vida3 was higher than 60% throughout the entire developmental period ( Arrighi et al, 2002 ). The antimalarial activity of Vida3 was associated to blockage of Plasmodium oocyst development, and the peptide was further found as toxic to Anopheles gambiae cells at 25 μM ( Carter et al, 2013 ).…”

An extensive computational approach to inhibit MSP-1 ofP.vivaxelucidates further horizon in the establishment next generation therapeutics against malaria

“…These organisms are thus a promising source for the prospection of anti-parasitic compounds, as alternative methods for the treatment of protozoa-related diseases [31] . Among the molecules already isolated and investigated, there are proteins and peptides with high activity against parasites, able to inhibit parasite activity in different stages of development [32], [33], [34]. Although, studies are still taking their first steps, initial results show new perspectives on the treatment of parasitic diseases.…”