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The role of the PI3K/Akt/FoxO pathway in the modulation of the midgut microbial diversity of Aedes aegypti

Grant number: 18/14760-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2018
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Jayme Augusto de Souza-Neto
Grantee:Pedro Henrique de Andrade Affonso
Home Institution: Instituto de Biotecnologia (IBTEC). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated research grant:13/11343-6 - Characterization of the microbiota-mediated anti-dengue mechanisms in wild Aedes aegypti populations, AP.JP
Associated scholarship(s):18/23231-1 - Construction of CRISPR-Cas9 plasmids to dissect the PI3K/Akt/FoxO pathway in Aedes Aegypti, BE.EP.IC

Abstract

Aedes aegypti is one of the most concerning urban emerging species to the public health Brazilian sector, once it is vector of viruses responsible for chikungunya, zika and dengue diseases. Current, the applied efforts against those diseases are mainly focuses in symptomatic treatments or prophylactic methods, since there is no vaccines or drugs efficient enough to be widely distributed. Therefore, the discovery of new modulation parameters able to affect immunological pathways behavior against the viruses-vectors interactions are important targets to new studies. One of the most recent, but very promising approaching tries to correlate insect viral susceptibility with its midgut symbiont microbiota.The PI3K/Akt/FoxO pathway in Drosophila melanogaster is one of the key pathways to its intestinal homeostasis maintenance, doing important modulation roles in the reactive oxygen species (ROS) production, in the expression of antimicrobial peptides (AMPs) independently of canonical pathways like Toll and Imd, and also being able to respond against RNA virus infections. Whereas relevant metabolic pathways are conserved between members of Diptera Order, the main objective of this research it is to evaluate the PI3K/Akt/FoxO pathway modulation influence in the bacterial microbiota of Ae. aegypti. Functional RNAi knockdown tests were made in the previous project using double-stranded RNA specific to Akt gene - the pathway negative regulator -, and to Lac Z gene as control group. Those tests revealed a strong modulation effect in the microbiota bacterial load and in to its diversity in akt knockdown groups. The results also presented the upregulation of Nitrogen Oxide Species (NOS) - an intermediary protein of ROS production cascate- and an upregulation of AMPs expression. Thus, those results demand complimentary investigation since them highlighted the hypothesis that PI3K/Akt/FoxO may be an relevant interference pathway in the hematological metabolization of Ae. aegypti, once as bloodfeed as the akt silencing tests are able to modulate the bacteria load and diversity by oxidative stress. Overall, this complimentary project would be able to evaluate how broad it is the PI3K/Akt/FoxO pathway influence in Ae. aegypti midgut homeostasis.