Last Updated: 18/06/2024
Mechanisms by which malaria parasites manipulate mosquito behaviour to enhance transmission
Objectives
The aim of the project is to demonstarte the mechanisms by which mosquitoes show greater attraction to humans infected with malaria parasites, and especially those carrying the stages capable of transmission to mosquitoes (gametocytes). It also will demonstrate why infective mosquitoes (carrying-sporozoites) behave more aggressively towards the human host.
The hypothesis to be tested, supported by preliminary data, is that increased attraction and stimulation of blood-feeding in mosquitoes is a result of a metabolite, (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), produced by parasites from the non-mevalonate pathway, which is absent in humans and mosquitoes. The research will involve (i) identification of gametocytes-metabolites using mass-spectrometry ; (ii) transcriptional-analyses of infected and infective mosquito ; (iii) behavioural studies on attraction to blood in a wind tunnel ; (iv) phagostimulation-analysis of mosquitoes offered gametocyte-metabolites ; (v) analysis of volatiles released from erythrocytes in response to gametocyte metabolites, that may mediate the behavioural changes, using gas chromatography–mass spectrometry (GC-MS) ; (vi) quantification of the volatiles released from breath vs. skin of gametocyte-carriers. The project findings will have practical use in understanding what makes mosquitoes preferentially bite infected individuals, become infected and transmit disease, and could lead to novel mosquito “lures” for traps. Overall the benefit would be reduced transmission of malaria in communities, with putative great impact on morbidity.
Jan 2018 — Dec 2021
$730,092
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