Overexpression of phosphatase and tensin homolog improves fitness and decreases Plasmodium falciparum development in Anopheles stephensi |
| |
| Institution: | 1. Department of Vector Biology and Control, State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Beijing 100071, China;2. Laboratory of Tropical Veterinary Medicine and Vector Biology, and Hainan Key Laboratory of Sustainable Utilization of Tropical Bioresources, Institute of Tropical Agriculture and Forestry, Hainan University, Hainan 570228, China;3. Department of Vector Control and Prevention, Hainan Provincial Center for Disease Prevention and Control, Hainan 570203, China;1. Laboratório Integrado de Bioquímica Hatisaburo Masuda (NUPEM), Universidade Federal do Rio de Janeiro (UFRJ), Campus Macaé, Macaé, RJ, Brazil;2. Laboratório de Sanidade Animal/CCTA, Unidade de Experimentação Animal, Laboratório de Biotecnologia/CBB, Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF), Campos dos Goytacazes, RJ, Brazil;3. Centro de Biotecnologia and Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil |
| |
| 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. |
| |
| Keywords: | Phosphatase and tensin homolog (PTEN) Mosquito Insulin/insulin-like growth factor signaling (IIS) Malaria |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
