Exploring Insect Models Physiology Through Microbial and Venom Derived Challenges

Abstract

The gut microbiome plays a major role in promoting organismal homeostasis. Mosquito microbiota influences various aspects of host physiology such as immunity, development and vector competence. Most studies addressing mosquito microbiota are based on laboratory-reared individuals and remain largely descriptive, consisting of microbial diversity profiling with limited investigation into the functional effects of individual bacteria on host physiology. In this context, our first aim was to characterize the bacterial flora of local wild mosquitoes and its effects on midgut homeostasis and immunity. While performing this study, we identified a pathogenic strain of Aeromonas hydrophila, accidentally introduced into the insectary, that causes mortality to both Culex pipiens and Aedes albopictus mosquitoes upon ingestion. In addition, we showed that A. hydrophila breaches the gut epithelium and gains access to the hemolymph. Parallel to gut damage, we detected a significant increase in the number of proliferative cells in the midguts of A. hydrophila-fed mosquitoes. Moreover, we found that this bacterium induces a local immune response in the gut leading to the production of anti-microbial peptides. Finally, whole genome sequencing of the isolated strain revealed that it possesses an arsenal of virulence and resistance genes, which provides mechanistic insights into its mosquitocidal activity. In the second part of the project, we aimed to explore how natural toxins, specifically scorpion venom, affect insects’ physiology. While the venoms of many Buthidae scorpions have been extensively studied for their toxicity and therapeutic potential, Hottentotta judaicus scorpion venom (HjSV) remains poorly explored. Using LC-ESI-MS, we showed that HjSV has a complex composition. In addition, we found that HjSV has no cytotoxic effects on three human cancer cell lines, even at high concentrations. However, it exerts a dose-dependent insecticidal effect against Drosophila melanogaster as well as A. albopictus and C. pipiens mosquitoes. These findings highlight the venom’s selective activity and reveal a species-dependent susceptibility in insects, with mosquitoes being more sensitive than Drosophila. Furthermore, we show that at sub-lethal doses, HjSV alters D. melanogaster behavioral patterns, by significantly reducing locomotor activity and increasing sleep duration. Altogether, our findings provide new insights into how microbial and venom-derived factors can modulate insect physiology, which may contribute, in the long term, to the development of new vector control strategies.