title: Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi.
abstract: The insulin/insulin-like growth factor signaling (IIS) cascade is highly conserved and regulates diverse physiological processes such as metabolism, lifespan, reproduction and immunity. Transgenic overexpression of Akt, a critical regulator of IIS, was previously shown to shorten mosquito lifespan and increase resistance to the human malaria parasite Plasmodium falciparum. To further understand how IIS controls mosquito physiology and resistance to malaria parasite infection, we overexpressed an inhibitor of IIS, phosphatase and tensin homolog (PTEN), in the Anopheles stephensi midgut. PTEN overexpression inhibited phosphorylation of the IIS protein FOXO, an expected target for PTEN, in the midgut of A. stephensi. Further, PTEN overexpression extended mosquito lifespan and increased resistance to P. falciparum development. The reduction in parasite development did not appear to be due to alterations in an innate immune response, but rather was associated with increased expression of genes regulating autophagy and stem cell maintenance in the midgut and with enhanced midgut barrier integrity. In light of previous success in genetically targeting the IIS pathway to alter mosquito lifespan and malaria parasite transmission, these data confirm that multiple strategies to genetically manipulate IIS can be leveraged to generate fit, resistant mosquitoes for malaria control.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Hauck
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Antonova-Koch
authors.forename: Anna
authors.initials: A
authors.lastname: Drexler
authors.forename: Jose
authors.initials: J
authors.lastname: Pietri
authors.forename: Nazzy
authors.initials: N
authors.lastname: Pakpour
authors.forename: Darin
authors.initials: D
authors.lastname: Liu
authors.forename: Jacob
authors.initials: J
authors.lastname: Blacutt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Riehle
authors.forename: Shirley
authors.initials: S
authors.lastname: Luckhart
mesh_terms: D000818:Animals; D000852:Anopheles / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D060829:Arthropod Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D005260:Female; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D008136:Longevity; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology; D013234:Stem Cells / Q000502:physiology
chemical_list: D060829:Arthropod Proteins; D051059:PTEN Phosphohydrolase
keywords: Anopheles stephensi; Insulin/insulin-like growth factor signaling (IIS); Malaria; Mosquito; Phosphatase and tensin homolog (PTEN); Plasmodium falciparum