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Streamlined SMFA and mosquito dark-feeding regime significantly improve malaria transmission-blocking assay robustness and sensitivity

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Title: Streamlined SMFA and mosquito dark-feeding regime significantly improve malaria transmission-blocking assay robustness and sensitivity
Authors: Habtewold, T
Tapanelli, S
Ellen KG, M
Astrid, H
Nikolai, W
George K, C
Item Type: Journal Article
Abstract: Background The development of malaria transmission-blocking strategies including the generation of malaria refractory mosquitoes to replace the wild populations through means of gene drives hold great promise. The standard membrane feeding assay (SMFA) that involves mosquito feeding on parasitized blood through an artificial membrane system is a vital tool for evaluating the efficacy of transmission-blocking interventions. However, despite the availability of several published protocols, the SMFA remains highly variable and broadly insensitive. Methods The SMFA protocol was optimized through coordinated culturing of Anopheles coluzzii mosquitoes and Plasmodium falciparum parasite coupled with placing mosquitoes under a strict dark regime before, during, and after the gametocyte feed. Results A detailed description of essential steps is provided toward synchronized generation of highly fit An. coluzzii mosquitoes and P. falciparum gametocytes in preparation for an SMFA. A dark-infection regime that emulates the natural vector-parasite interaction system is described, which results in a significant increase in the infection intensity and prevalence. Using this optimal SMFA pipeline, a series of putative transmission-blocking antimicrobial peptides (AMPs) were screened, confirming that melittin and magainin can interfere with P. falciparum development in the vector. Conclusion A robust SMFA protocol that enhances the evaluation of interventions targeting human malaria transmission in laboratory setting is reported. Melittin and magainin are identified as highly potent antiparasitic AMPs that can be used for the generation of refractory Anopheles gambiae mosquitoes.
Issue Date: 25-Jan-2019
Date of Acceptance: 19-Jan-2019
URI: http://hdl.handle.net/10044/1/67187
DOI: https://dx.doi.org/10.1186/s12936-019-2663-8
ISSN: 1475-2875
Publisher: BioMed Central
Journal / Book Title: Malaria Journal
Volume: 18
Copyright Statement: © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Wellcome Trust
Bill & Melinda Gates Foundation
Funder's Grant Number: 107983/Z/15/Z
OPP1158151
Keywords: Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Parasitology
Tropical Medicine
Anopheles coluzzii
Anopheles gambiae
Plasmodium falciparum
Malaria
Gametocyte
Standard membrane feeding assay
Mosquito population replacement
Gene drive
PLASMODIUM-FALCIPARUM GAMETOCYTES
GENE DRIVE
REQUIREMENTS
MAGAININS
PARASITES
VECTORS
SYSTEMS
Animals
Anopheles
Antimalarials
Communicable Disease Control
Feeding Behavior
Genetic Engineering
Malaria, Falciparum
Mosquito Vectors
Peptides
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN 24
Appears in Collections:Faculty of Natural Sciences



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