The mosquito salivary gland is critical for successful blood-feeding and pathogen transmission, suggesting that mechanisms to disrupt salivary gland function is likely to reduce blood feeding capabilities and reduce mosquito vectorial capacity. However, mosquito salivary gland physiology is poorly understood, which restricts the development of novel insecticides targeting salivary gland function. Thus, we aimed to determine the impact of neuroendocrine systems and inhibitors of potassium ion channels to the secretory activity of Aedes aegypti salivary gland. Dopamine (DA) was shown to be the most potent neuromodulator (EC50: 28 µM), followed by serotonin (EC50: 34 µM), and the least potent was pilocarpine (EC50: 1.1mM). Various selective inhibitors of DA receptor inhibitors, such as itopride and fluphenazine, significantly reduced fluid secretion, indicating salivation is likely mediated by a dopaminergic pathway. Next, we studied the impact of ATP-sensitive inward rectifier potassium (KATP) channels to fluid secretion because these channels have been linked to salivary gland function in other arthropods. Data show that the chemical activation of KATP channels with pinacidil or VU0071063 reduced salivary secretion by 5-fold when compared to control mosquitoes. Importantly, inclusion of pinacidil and VU0071063 into a blood meal reduced blood ingestion by approximately 97%, indicating reduced salivary gland activity is correlated to reduced blood feeding capabilities. The reduced blood feeding capabilities led us to hypothesize that acquisition of a pathogen during blood feeding would also be reduced. Indeed, mosquitoes that fed blood meals incorporated with Chikungunya virus and pinacidil had significantly (P&lt;0.0001) less virus than control mosquitoes. Importantly, all mosquitoes that fed on meals treated with KATP activators did not disseminate the virus 13 days post-infection and thus, 0% of mosquitoes became competent vectors. These data provide significant evidence that KATP channels represent a putative target site for the interruption of mosquito blood feeding and pathogen transmission.

Identification of novel target sites to reduce salivary gland function and feeding of Aedes aegypti

2019 Fall National Meeting

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