AMPK and PTP‐1B stand at the gates of immunity, metabolism and egg formation in mosquitoes. (LB224)

Abstract

Mosquitoes are major vectors of human diseases. This is mainly due to their requirement for a blood meal to lay eggs which allows the transmission of pathogens to the human being. Our aim is to identify proper molecular targets in order to block blood feeding and impair egg formation. In their early days of adult life mosquitoes feed on vegetal fluids and their midgut is continuously loaded with several bioactive compounds including polyphenols. We observed that polyphenol‐fed mosquitos dramatically increase their average lifespan (Control T 1/2 ± 15‐18 days, Polyphenol‐fed T1/2± 20‐32 days). Polyphenols also reduced the body triglyceride content from 20‐75 %. They trigger midgut autophagy which leads to a 40 % decrease on bacterial loads. Such mechanisms are mimicked by the activation of the mosquito AMPK and abolished by RNAi‐mediated silencing of this gene. Thus the presence of polyphenol on early mosquito meals optimizes mosquito metabolism and immunity and its chances of finding its first blood meal. After a blood meal digestion will take place in mosquito midgut. Blood‐derived nutrients allow yolk synthesis and egg formation. Blood feeding affects the expression of the mosquito PTP‐1B (AaPTP1B) in tissues critically involved in the synthesis and storage of vitellogenin (Vg), the major yolk protein. The protein tyrosine phosphatase inhibitor sodium orthovanadate or the PTP substrate DiFMUP decreased Vg synthesis and egg production. Also, silencing of AaPTP1B using by RNAi assays suppressed by 30 % egg production. In conclusion, the above results show that mosquito signaling pathways regulated by AMPK and PTP1B are proper targets to block blood feeding and egg formation. Future research strategies should be designed to generate novel cell signaling‐based insecticides that simultaneously decrease mosquito lifespan and reproduction. Grant Funding Source: Supported by CNPq, INCT‐EM, FAPERJ