Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes

PLoS Pathogens

Frank Ramberg¹  Vanessa Corby-Harris¹  Laurel Watkins de Jong¹  Yevgeniya Antonova¹  Rolf Ziegler¹  Shirley Luckhart¹  Edwin E. Lewis²  Jessica M. Brown³  Anna Drexler⁴  Michael A. Riehle⁴  Nazzy Pakpour⁴ 

[1] Department of Entomology, University of Arizona, Tucson, Arizona, United States of America;Department of Entomology, University of California – Davis, Davis, California, United States of America;Department of Nematology, University of California – Davis, Davis, California, United States of America;Medical Microbiology and Immunology, University of California – Davis, Davis, California, United States of America

关键词: Mosquitoes;    Parasitic diseases;    Malarial parasites;    Plasmodium;    Malaria;    Oocysts;    Insulin;    AKT signaling cascade;   

DOI  :  10.1371/journal.ppat.1001003

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60–99%. Of those mosquitoes that were infected, we observed a 75–99% reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18–20% reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity.

【 授权许可】

CC BY