Use of a Drosophila model to identify genes regulating Plasmodium growth in the mosquito.
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.
Brandt
Stephanie M
SM
Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA.
Jaramillo-Gutierrez
Giovanna
G
Kumar
Sanjeev
S
Barillas-Mury
Carolina
C
Schneider
David S
DS
D000818:Animals; D000852:Anopheles / Q000276:immunology / Q000469:parasitology*; D004330:Drosophila / Q000235:genetics* / Q000276:immunology / Q000469:parasitology*; D029721:Drosophila Proteins / Q000235:genetics*; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000635:transmission*; D009154:Mutation / Q000235:genetics; D010961:Plasmodium / Q000235:genetics / Q000254:growth & development* / Q000276:immunology; D015996:Survival Rate
D029721:Drosophila Proteins
Parasitology. 1997 Jul;115 ( Pt 1):1-7
9280891
Int J Parasitol. 2003 Aug;33(9):933-43
12906877
PLoS Biol. 2004 Dec;2(12):e418
15562316
Curr Biol. 2002 Oct 15;12(20):1728-37
12401167
Nat Rev Immunol. 2007 Nov;7(11):862-74
17948019
Nature. 1981 May 21;291(5812):238-9
7015147
Science. 2000 Jun 30;288(5475):2376-9
10875925
PLoS Pathog. 2006 Jun;2(6):e52
16789837
Genetics. 2008 Mar;178(3):1807-15
18245331
J Exp Med. 1988 Apr 1;167(4):1459-71
2833557
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14139-44
14623973
Biotechniques. 2000 Jul;29(1):52, 54
10907076
Cell. 2001 Mar 9;104(5):709-18
11257225
Cell Microbiol. 2003 Dec;5(12):901-11
14641175
Cell Microbiol. 2007 Dec;9(12):2775-83
17883424
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11420-5
16076953
Science. 2002 Oct 4;298(5591):149-59
12364792
Genetics. 2001 Sep;159(1):189-99
11560896