Phagostimulatory dynamics of adenine nucleotides in mosquitoes : advancing a taste-based delivery method for vector control agents

Abstract: The mosquitoes Aedes aegypti and Anopheles gambiae are vectors of major medical importance, incriminated in over half a million lives lost annually. While there has been significant focus on understanding the olfaction mechanisms underlying host-seeking in mosquitoes for the development of odour-based control tools, little is known about the mechanisms underlying gustation in blood feeding, the ultimate behaviour in the change of events leading up to disease transmission. An increased understanding of these gustatory mechanisms may be vital for advancing taste-based alternative vector control tools. Using a no-choice membrane feeding assay (papers II, III, and IV) and a spectrophotometric analysis (paper II), the feeding response of the two vectors to blood-derived adenine nucleotide diets, as proxies, and a reliable signal, for blood, was examined. While these experiments revealed that Ae. aegypti is more sensitive than An. gambiae (paper II) to the adenine nucleotide diets, both species maintained the same selectivity to the diets, with a dose-dependent bimodal feeding pattern. The latter expands the all-or-none blood-feeding theory for haematophagous arthropods to include an initial tasting step (paper II). Adenine nucleotides also regulated the proportion of An. gambiae prediuresing in a dose-dependent manner, but did not affect the volume engorged or prediuresed (paper II). A transcriptome analysis of the labrum identified putative genes that are involved in the detection and assessment of blood modalities (paper III). A shift from a high abundance of genes with structural function in the teneral age libraries to genes with cellular, neuro-communicative and modulatory function, including putative ATP receptors, in the 3 days-post-eclosion libraries was observed, providing blood feeding mosquitoes with a structurally sturdy and chemosensory-competent blood feeding organ (paper IV).  The assessment of whether the ATP sensory pathway may be a viable way of overcoming the aversive effects of antifeedants and toxicants revealed its superiority over the sugar sensory pathway. ATP induced a reflexive engorgement on toxic meals, which were directed to the midgut, in contrast to sugar-induced meals, which were directed to the crop, an observation that correlated with the rapid mortality rates. Taken together, this study expanded our mechanistic understanding of the phagostimulatory dynamics of adenine nucleotides in Ae. aegypti and An. gambiae, and the associated putative labral detection receptors in Ae. aegypti, with the establishment of a novel workflow for advancing taste-based vector control tools.