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Phenylalanine Metabolism Regulates Reproduction and Parasite Melanization in the Malaria Mosquito

Title: Phenylalanine Metabolism Regulates Reproduction and Parasite Melanization in the Malaria Mosquito
Authors: Fuchs, S
Behrends, V
Bundy, JG
Crisanti, A
Nolan, T
Item Type: Journal Article
Abstract: The blood meal of the female malaria mosquito is a pre-requisite to egg production and also represents the transmission route for the malaria parasite. The proper and rapid assimilation of proteins and nutrients in the blood meal creates a significant metabolic challenge for the mosquito. To better understand this process we generated a global profile of metabolite changes in response to blood meal of Anopheles gambiae, using Gas Chromatography-Mass Spectrometry (GC-MS). To disrupt a key pathway of amino acid metabolism we silenced the gene phenylalanine hydroxylase (PAH) involved in the conversion of the amino acid phenylalanine into tyrosine. We observed increased levels of phenylalanine and the potentially toxic metabolites phenylpyruvate and phenyllactate as well as a reduction in the amount of tyrosine available for melanin synthesis. This in turn resulted in a significant impairment of the melanotic encapsulation response against the rodent malaria parasite Plasmodium berghei. Furthermore silencing of PAH resulted in a significant impairment of mosquito fertility associated with reduction of laid eggs, retarded vitellogenesis and impaired melanisation of the chorion. Carbidopa, an inhibitor of the downstream enzyme DOPA decarboxylase that coverts DOPA into dopamine, produced similar effects on egg melanization and hatching rate suggesting that egg chorion maturation is mainly regulated via dopamine. This study sheds new light on the role of amino acid metabolism in regulating reproduction and immunity.
Issue Date: 7-Jan-2014
Date of Acceptance: 20-Nov-2013
URI: http://hdl.handle.net/10044/1/40729
DOI: http://dx.doi.org/10.1371/journal.pone.0084865
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLOS One
Volume: 9
Issue: 1
Copyright Statement: © 2014 Fuchs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
ANOPHELES-GAMBIAE
AEDES-AEGYPTI
EGG DEVELOPMENT
AMINO-ACIDS
MELANOTIC ENCAPSULATION
DOPA DECARBOXYLASE
IMMUNE-RESPONSES
GENES
EXPRESSION
INFUSION
Animals
Culicidae
Enzyme Activation
Feeding Behavior
Female
Fertility
Gene Knockdown Techniques
Gene Silencing
Malaria
Metabolic Networks and Pathways
Metabolome
Phenotype
Phenylalanine
Phenylalanine Hydroxylase
Reproduction
General Science & Technology
MD Multidisciplinary
Publication Status: Published
Article Number: e84865
Appears in Collections:Division of Surgery
Faculty of Medicine
Faculty of Natural Sciences



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