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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Killer Bee Molecules: Antimicrobial Peptides as Effector Molecules to Target Sporogonic Stages of Plasmodium
PLoS Pathogens, Volume 9, No. 11, Article e1003790, Year 2013
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Description
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. © 2013 Carter et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3836994/bin/ppat.1003790.s001.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3836994/bin/ppat.1003790.s002.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3836994/bin/ppat.1003790.s003.doc
Authors & Co-Authors
Carter, Victoria
United Kingdom, Keele
Keele University
Underhill, Ann
United Kingdom, Keele
Keele University
Baber, Ibrahima
Mali, Bamako
Université Des Sciences
Sylla, Lakamy
Mali, Bamako
Université Des Sciences
Baby, Mounirou A.
Mali, Bamako
Centre National de Transfusion Sanguine
Thiéry, Isabelle
France, Paris
Institut Pasteur, Paris
Zettor, Agnès
France, Paris
Institut Pasteur, Paris
Bourgouin, Catherine
France, Paris
Institut Pasteur, Paris
Langel, Ülo
Sweden, Stockholm
Stockholms Universitet
Faye, Ingrid
Sweden, Stockholm
Institutionen För Molekylär Biovetenskap, Wenner-grens Institut
Otvos, Laszlo
United States, Philadelphia
Temple University
Wade, John D.
Australia, Melbourne
University of Melbourne
Coulibaly, Mamadou B.
Mali, Bamako
Université Des Sciences
Traoré, Sékou Fantamady
Mali, Bamako
Université Des Sciences
Tripét, Frédéric R.
United Kingdom, Keele
Keele University
Eggleston, Paul
United Kingdom, Keele
Keele University
Hurd, Hilary
United Kingdom, Keele
Keele University
Statistics
Citations: 52
Authors: 17
Affiliations: 8
Identifiers
Doi:
10.1371/journal.ppat.1003790
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Environmental
Infectious Diseases
Study Locations
Multi-countries
Mali