Originally published as Genetics Published Articles Ahead of Print on September 14, 2008.

Genetics, Vol. 180, 1671-1678, November 2008, Copyright © 2008
doi:10.1534/genetics.108.089748

Use of a Drosophila Model to Identify Genes Regulating Plasmodium Growth in the Mosquito

Stephanie M. Brandt^*,1, Giovanna Jaramillo-Gutierrez, Sanjeev Kumar, Carolina Barillas-Mury and David S. Schneider^*,2

^* Department of Microbiology and Immunology, Stanford University, Stanford, California 94305 and Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20892-8130

² Corresponding author: D333 Fairchild Bldg., 299 Campus Dr., Stanford University, Stanford, CA 94305-5124. 
E-mail: dschneider{at}stanford.edu

We performed a forward genetic screen, using Drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, Plasmodium gallinaceum. We identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. Presumptive mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. None of the identified genes have been previously implicated in innate immune responses or interactions with Plasmodium. The functions of five Anopheles gambiae homologs were tested by using RNAi to knock down gene function followed by measuring the growth of the rodent parasite, Plasmodium berghei. Loss of function of four of these genes in the mosquito affected Plasmodium growth, suggesting that Drosophila can be used effectively as a surrogate mosquito to identify relevant host factors in the mosquito.

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