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Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa

Mendes, AM; Schlegelmilch, T; Cohuet, A; Awono-Ambene, P; De Iorio, M; Fontenille, D; Morlais, I; ... Vlachou, D; + view all (2008) Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa. PLOS PATHOG , 4 (5) , Article e1000069. 10.1371/journal.ppat.1000069. Green open access

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Abstract

In much of sub-Saharan Africa, the mosquito Anopheles gambiae is the main vector of the major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of P. berghei development are also pertinent to A. gambiae/P. falciparum interactions in semi-natural conditions, using field isolates of this parasite and geographically related mosquitoes. We detected broadly similar albeit not identical transcriptional responses of these genes to the two parasite species. Gene silencing established that two genes affect similarly both parasites: infections are hindered by the intracellular local activator of actin cytoskeleton dynamics, WASP, but promoted by the hemolymph lipid transporter, ApoII/I. Since P. berghei is not a natural parasite of A. gambiae, these data suggest that the effects of these genes have not been drastically altered by constant interaction and co-evolution of A. gambiae and P. falciparum; this conclusion allowed us to investigate further the mode of action of these two genes in the laboratory model system using a suite of genetic tools and infection assays. We showed that both genes act at the level of midgut invasion during the parasite's developmental transition from ookinete to oocyst. ApoII/I also affects the early stages of oocyst development. These are the first mosquito genes whose significant effects on P. falciparum field isolates have been established by direct experimentation. Importantly, they validate for semi-field human malaria transmission the concept of parasite antagonists and agonists.

Type: Article
Title: Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.ppat.1000069
Publisher version: http://dx.doi.org/10.1371/journal.ppat.1000069
Language: English
Additional information: © 2008 Mendes 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. Funding: The work was supported by a UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) grant (A50241), a NIAID-NIH Programme Project grant (2PO1AI044220-06A1), the BioMalPar European Network of Excellence grant (LSHP-CT-2004-503578) from Priority 1 “Life Sciences, Genomics and Biotechnology for Health” in the 6th Framework Programme, and a Wellcome Trust Programme grant (GR077229/Z/05/Z).
Keywords: MOSQUITO ANOPHELES-GAMBIAE, QUANTITATIVE TRAIT LOCI, MALARIA VECTOR, EXPERIMENTAL INFECTIONS, GALLERIA-MELLONELLA, GAMETOCYTE CARRIERS, APOLIPOPHORIN-III, IMMUNE-RESPONSE, MIDGUT INVASION, LIPID TRANSPORT
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Statistical Science
URI: https://discovery.ucl.ac.uk/id/eprint/1360517
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