TY - JOUR
T1 - Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi
AU - Hauck, Eric S.
AU - Antonova-Koch, Yevgeniya
AU - Drexler, Anna
AU - Pietri, Jose
AU - Pakpour, Nazzy
AU - Liu, Darin
AU - Blacutt, Jacob
AU - Riehle, Michael A.
AU - Luckhart, Shirley
N1 - Funding Information:
We would like to thank Kong Cheung and Molly Mulleague for assistance with these studies. Funding was provided by the National Institutes of Health National Institute for Allergy and Infectious Diseases to MAR and SL ( AI073745 ).
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Anopheles stephensi
KW - Insulin/insulin-like growth factor signaling (IIS)
KW - Malaria
KW - Mosquito
KW - Phosphatase and tensin homolog (PTEN)
KW - Plasmodium falciparum
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U2 - 10.1016/j.micinf.2013.05.006
DO - 10.1016/j.micinf.2013.05.006
M3 - Article
C2 - 23774695
AN - SCOPUS:84884704110
SN - 1286-4579
VL - 15
SP - 775
EP - 787
JO - Microbes and Infection
JF - Microbes and Infection
IS - 12
ER -