Abstract
Plasmodium invasion of mosquito midguts is a mandatory step for malaria transmission. The roles of mosquito midgut proteins and parasite interaction during malaria transmission are not clear. This study aims to identify mosquito midgut proteins that interact with and affect P. falciparum invasion. Based on gene expression profiles and protein sequences, 76 mosquito secretory proteins that are highly expressed in midguts and up-regulated by blood meals were chosen for analysis. About 61 candidate genes were successfully cloned from Anopheles gambiae and expressed in insect cells. ELISA analysis showed that 25 of the insect cell-expressed recombinant mosquito proteins interacted with the P. falciparum-infected cell lysates. Indirect immunofluorescence assays confirmed 17 of them interacted with sexual stage parasites significantly stronger than asexual stage parasites. Knockdown assays found that seven candidate genes significantly changed mosquitoes' susceptibility to P. falciparum. Four of them (AGAP006268, AGAP002848, AGAP006972, and AGAP002851) played a protective function against parasite invasion, and the other three (AGAP008138, FREP1, and HPX15) facilitated P. falciparum transmission to mosquitoes. Notably, AGAP008138 is a unique gene that only exists in Anopheline mosquitoes. These gene products are ideal targets to block malaria transmission.
Highlights
Plasmodium falciparum interaction reveals mosquito genes important for malaria transmission Yingjun Cui, Guodong Niu, Vincent L
In order to find mosquito proteins that affect malaria transmission to mosquitoes in midguts, we used four criteria to select candidates: 1) the proteins have signal peptides; 2) the genes express higher in the midgut than in any other tissues (> 1.2-fold); 3) the genes are up-regulated 3 h after a blood meal (> 1.2-fold), and 4) the expression of the genes return to the regular level 24 h after a blood meal
It is essential for Plasmodium parasites to infect mosquitoes to complete a malaria transmission cycle
Summary
Plasmodium falciparum interaction reveals mosquito genes important for malaria transmission Yingjun Cui, Guodong Niu, Vincent L. A sexual stage parasite attaches PM and penetrate two physical barriers, the PM and epithelium, to reach the basal lamina, where it develops into an oocyst During this infection process, the molecular interaction between mosquito midgut proteins and sexual stage parasites, e.g., gametocytes or ookinetes, directly affects malaria transmission. These transmission-blocking targets share some common biochemical features, such as higher abundance in the midgut than in other tissues, the induction of expression immediately after a blood m eal[12], and direct access to large molecules such as Ab in human blood Based on these features, we chose mosquito genes that are up-regulated three hours after a blood meal, and their products have signal peptides. Five novel proteins related to malarial transmission were discovered These genes and their products are promising targets for transmission-blocking vaccines, drugs, or transgenic mosquitoes for malaria control
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