Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FREP1 in mosquito midguts facilitates Plasmodium falciparum parasite transmission. The fibrinogen-like (FBG) domain of FREP1 is highly conserved (>90% identical) among Anopheles species from different continents, suggesting that anti-FBG antibodies may block malaria transmission to all anopheline mosquitoes. Using standard membrane-feeding assays, anti-FREP1 polyclonal antibodies significantly blocked transmission of Plasmodium berghei and Plasmodium vivax to Anopheles gambiae and Anopheles dirus, respectively. Furthermore, in vivo studies of mice immunized with FBG achieved >75% blocking efficacy of P. berghei to A. gambiae without triggering immunopathology. Anti-FBG serum also reduced >81% of P. falciparum infection to A. gambiae Finally, we showed that FBG interacts with Plasmodium gametocytes and ookinetes, revealing the molecular mechanism of its antibody transmission-blocking activity. Collectively, our data support that FREP1-mediated Plasmodium transmission to mosquitoes is a conserved pathway and that targeting the FBG domain of FREP1 will limit the transmission of multiple Plasmodium species to multiple Anopheles species.
 ...
PMID:The fibrinogen-like domain of FREP1 protein is a broad-spectrum malaria transmission-blocking vaccine antigen. 2853 29

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.
 ...
PMID:Analysis of blood-induced Anopheles gambiae midgut proteins and sexual stage Plasmodium falciparum interaction reveals mosquito genes important for malaria transmission. 3286 41