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Title: Analysis of blood-induced Anopheles gambiae midgut proteins and sexual stage Plasmodium falciparum interaction reveals mosquito genes important for malaria transmission
Abstract

Plasmodiuminvasion 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 affectP. falciparuminvasion. 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 fromAnopheles gambiaeand expressed in insect cells. ELISA analysis showed that 25 of the insect cell-expressed recombinant mosquito proteins interacted with theP. 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 toP. falciparum. Four of them (AGAP006268, AGAP002848, AGAP006972, and AGAP002851) played a protective function against parasite invasion, and the other three (AGAP008138, FREP1, and HPX15) facilitatedP. falciparumtransmission to mosquitoes. Notably, AGAP008138 is a unique gene that only exists inAnophelinemosquitoes. These gene products are ideal targets to block malaria transmission.

 
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NSF-PAR ID:
10188677
Author(s) / Creator(s):
; ; ; ;
Publisher / Repository:
Nature Publishing Group
Date Published:
Journal Name:
Scientific Reports
Volume:
10
Issue:
1
ISSN:
2045-2322
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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