Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.

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...

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Auteurs principaux:	Silke Fuchs, Volker Behrends, Jacob G Bundy, Andrea Crisanti, Tony Nolan
Format:	article
Langue:	EN
Publié:	Public Library of Science (PLoS) 2014
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/6edeb0f98cd14d25be9bc5b6bc303fd5
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spelling	oai:doaj.org-article:6edeb0f98cd14d25be9bc5b6bc303fd52021-11-18T08:38:45ZPhenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.1932-620310.1371/journal.pone.0084865https://doaj.org/article/6edeb0f98cd14d25be9bc5b6bc303fd52014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24409310/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Silke FuchsVolker BehrendsJacob G BundyAndrea CrisantiTony NolanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84865 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silke Fuchs Volker Behrends Jacob G Bundy Andrea Crisanti Tony Nolan Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.
description	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.
format	article
author	Silke Fuchs Volker Behrends Jacob G Bundy Andrea Crisanti Tony Nolan
author_facet	Silke Fuchs Volker Behrends Jacob G Bundy Andrea Crisanti Tony Nolan
author_sort	Silke Fuchs
title	Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.
title_short	Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.
title_full	Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.
title_fullStr	Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.
title_full_unstemmed	Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.
title_sort	phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6edeb0f98cd14d25be9bc5b6bc303fd5
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Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.

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