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

PLoS Pathogens

Mounirou Baby¹  Frederic Tripet²  Paul Eggleston²  Hilary Hurd²  Victoria Carter²  Ann Underhill²  Ingrid Faye³  Ülo Langel⁴  John D. Wade⁵  Agnès Zettor⁶  Catherine Bourgouin⁶  Isabelle Larget-Thiery⁶  Lakamy Sylla⁷  Ibrahima Baber⁷  Mamadou B. Coulibaly⁷  Sekou F. Traore⁷  Laszlo Otvos⁸ 

[1] Centre National de Transfusion Sanguine, Bamako, Mali;Centre for Applied Entomology and Parasitology, School of Life Sciences, Keele University, Keele, Staffordshire, United Kingdom;Department of Molecular Bioscience, the Wenner-Gren Institute, Svante Arrhenius v. 20C, Stockholm University, Stockholm, Sweden;Department of Neurochemistry Svante Arrhenius v. 21A, Stockholm University, Stockholm, Sweden;Howard Florey Research Laboratories, Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia;Institut Pasteur, Centre for Production and Infection of Anopheles (CEPIA), Parasitology and Mycology Department, Paris, France;Malaria Research and Training Centre (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako, Bamako, Mali;Temple University Department of Biology, Philadelphia, Pennsylvania, United States of America

关键词: Mosquitoes;    Plasmodium;    Dimers (Chemical physics);    Malarial parasites;    Malaria;    Blood;    Gametocytes;    Oocysts;   

DOI  :  10.1371/journal.ppat.1003790

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY