Insecticide resistance and population dynamics of medically important insects: developmental analysis, mechanism investigation, modeling prediction, and bioinformatics characterization

Abstract

Mosquitoes, particularly the Aedes species, are notorious pests that transmit various human and animal pathogens, including plasmodium, flavivirus (e.g. dengue virus), alphavirus(e.g. chikungunya virus), and filarial worms. These mosquito-borne diseases have affected millions of people worldwide, requiring urgent control and prevention measures. The key to cutting the transmission of mosquito-borne diseases is to manage the mosquito population. Mosquito population surveillance and predication are the prerequisites for effective mosquito management. Environmental factors are important for the mosquito population dynamics, therefore understanding the relationship between mosquito populations dynamics and environmental factors is crucial for developing efficient models to investigate and predict their dynamics in the field. This knowledge helps optimize mosquito management strategies and prevent the spread of mosquito-borne diseases. In a comprehensive four-year study in Alabama, we identified four Aedes mosquito species, namely Aedes albopictus, Aedes triseriatus, Aedes japonicus, and Aedes aegypti, in Alabama. We evaluate the impact of different environmental factors such as temperature, day length, water vapor pressure, and wind speed on mosquito population dynamics through the random forest modelling. These factors were found to significantly influence mosquito population dynamics. Additionally, we employed the model to predict the distribution of mosquito populations in the southeastern United States, and hypothesized the relationship between the dynamics of mosquito populations and other factors like human density, elevation, and forest regions. Several methods have been employed to control mosquito populations, with insecticide spraying being the most widely used and effective approach. To assess the efficacy of insecticides, we evaluated the sensitivity/resistance status of both adult and larval Aedes albopictus samples collected from different locations in Alabama. Eight insecticides, including β-cyfluthrin, chlorpyrifos, deltamethrin, etofenprox, fenitrothion, permethrin, resmethrin, and malathion, were tested. Adult Aedes albopictus from all locations exhibited similar results regarding the time to 100% mortality and the diagnostic time in the CDC bottle bioassay. However, Aedes albopictus demonstrated prolonged survival beyond the diagnostic time for permethrin, fenitrothion, and resmethrin treatments. In the larval bioassay, malathion exhibited the least toxicity to Aedes albopictus, followed by resmethrin and etofenprox. Chlorpyrifos demonstrated the highest larval toxicity. The resistance status of Aedes albopictus from all locations remained similar to a previous survey conducted in 2004, suggesting slow development of resistance in this strain. However, Aedes albopictus from Tuskegee showed resistance to chlorpyrifos compared to a susceptible strain. The dose-response curves to most tested insecticides for these field populations of Aedes albopictus were similar to or slightly higher than those measured eighteen years prior, indicating relatively consistent responses to all insecticides tested. Aedes aegypti, another significant vector in human disease transmission, has developed resistance to commonly used insecticides, particularly pyrethroids and organophosphates, on a global scale. In this study, we evaluated the sensitivity/resistance to chlorpyrifos, fenitrothion, malathion, deltamethrin, permethrin, and β-cyfluthrin in three strains of Aedes aegypti mosquitoes. The results revealed that the resistant strain (PR) exhibited high levels of resistance to all three pyrethroid insecticides, with 6,500-fold, 3,200-fold, and 17,000-fold resistance to permethrin, β-cyfluthrin, and deltamethrin, respectively. The newly emerged Aedes aegypti population from St. Augustine, Florida (Aefl), displayed elevated levels of resistance to malathion (12-fold) and permethrin (25-fold). Synergists DEF and DEM had minimal effects on insecticide resistance in both Aefl and PR strains, while PBO completely abolished resistance to malathion and permethrin in Aefl and partially suppressed resistance in PR. Further examination of the voltage-gated sodium channel sequences in PR revealed two mutations (V1016G/I and F1534C substitutions) associated with pyrethroid resistance. These mutations were not identified in Aefl, indicating that cytochrome P450-mediated detoxification, along with target site insensitivity through mutations in the voltage-gated sodium channel, contributed to the high levels of resistance in the PR strain. In summary, the more efficient mosquito management strategy is important for controlling the transmission of mosquito-borne disease. Surveillance, understanding the factors influencing mosquito population, and predicting the mosquito population dynamic are essential for developing the mosquito management strategies. Additionally, assessing insecticide sensitivity/resistance and investigating the mechanisms behind resistance in different mosquito species are vital for optimizing control measures and preventing the spread of mosquito-borne diseases. To explore the future directions regarding the mechanisms of insecticide resistance, one potential approach is to utilize RNA sequencing (RNAseq) data to conduct a detailed analysis of single nucleotide polymorphisms (SNPs) in both resistant and susceptible strains. Subsequently, genetic editing tools such as CRISPR-Cas9 can be employed to further elucidate the functional significance of these SNPs.