Heat shock proteins, thermotolerance, and insecticide resistance in mosquitoes.

Mosquitoes transmit pathogens that pose a threat to millions of people globally. Unfortunately, widespread insecticide resistance makes it difficult to control these public health pests. General mechanisms of resistance, such as target site mutations or increased metabolic activity, are well established. However, many questions regarding the dynamics of these adaptations in the context of developmental and environmental conditions require additional exploration. One aspect of resistance that deserves further study is the role of heat shock proteins (HSPs) in insecticide tolerance. Studies show that mosquitoes experiencing heat stress before insecticide exposure demonstrate decreased mortality. This is similar to the observed reciprocal reduction in mortality in mosquitoes exposed to insecticide prior to heat stress. The environmental shifts associated with climate change will result in mosquitoes occupying environments with higher ambient temperatures, which could enhance existing insecticide resistance phenotypes. This physiological relationship adds a new dimension to the problem of insecticide resistance and further complicates the challenges that vector control and public health personnel face. This article reviews studies illustrating the relationship between insecticide resistance and HSPs or hsp genes as well as the intersection of thermotolerance and insecticide resistance. Further study of HSPs and insecticide resistance could lead to a deeper understanding of how environmental factors modulate the physiology of these important disease vectors to prepare for changing climatic conditions and the development of novel strategies to prevent vector-borne disease transmission.

Exploring the Wilderness within: An Integrative Metabolomics and Transcriptomics Study on Near-Wild and Colonized Aedes aegypti.

This study examines the phenotypic differences between wild-derived F2 Central Valley mosquitoes and the insecticide-susceptible Rockefeller (Rock) lab strain of Ae. aegypti. Given the rarity of wild pyrethroid-susceptible populations, the focus of this work is to develop an understanding of the resistance physiology in this invasive mosquito population and explore the potential of metabolites as diagnostic biomarkers for metabolic resistance. This study utilizes metabolomic, gene expression, and lifespan data for a comparison between strains. The findings indicate that wild-derived mosquitoes with greater metabolic resistance have a lifespan sensitivity to restricted larval nutrition. In terms of metabolism and gene expression, Central Valley mosquitoes show increased activity in oxidoreductase, glutathione metabolism, and the pentose phosphate pathway. Conversely, Rock mosquitoes display signs of metabolic inefficiency and mitochondrial dysregulation, likely tolerated due to the consistency and nutritional abundance of a controlled lab environment. The study also examines Ae. aegypti P450 and GSTE profiles in relation to other insecticide-resistant groups. While metabolomic data can differentiate our study groups, the challenges in biomarker development arise from few detected markers meeting high fold change thresholds.

Fat and Happy: Profiling Mosquito Fat Body Lipid Storage and Composition Post-blood Meal.

The fat body is considered the insect analog of vertebrate liver and fat tissue. In mosquitoes, a blood meal triggers a series of processes in the fat body that culminate in vitellogenesis, the process of yolk formation. Lipids are stored in the fat body in specialized organelles called lipid droplets that change in size depending on the nutritional and metabolic status of the insect. We surveyed lipid droplets in female Aedes aegypti fat body during a reproductive cycle using confocal microscopy and analyzed the dynamic changes in the fat body lipidome during this process using LC/MS. We found that lipid droplets underwent dynamic changes in volume after the mosquito took a blood meal. The lipid composition found in the fat body is quite complex with 117 distinct lipids that fall into 19 classes and sublcasses. Our results demonstrate that the lipid composition of the fat body is complex as most lipid classes underwent significant changes over the course of the vitellogenic cycle. This study lays the foundation for identifying unknown biochemical pathways active in the mosquito fat body, that are high-value targets for the development of novel mosquito control strategies.