Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparum Gametocytogenesis and Transmission to Mosquitoes.
Cell Rep
; 29(12): 3796-3806.e4, 2019 12 17.
Article
in En
| MEDLINE
| ID: mdl-31851913
Plasmodium falciparum gametocytes infect mosquitoes and are responsible for malaria transmission. New interventions that block transmission could accelerate malaria elimination. Gametocytes develop within erythrocytes and activate protein export pathways that remodel the host cell. Plasmepsin V (PMV) is an aspartyl protease that is required for protein export in asexual parasites, but its function and essentiality in gametocytes has not been definitively proven, nor has PMV been assessed as a transmission-blocking drug target. Here, we show that PMV is expressed and can be inhibited specifically in P. falciparum stage I-II gametocytes. PMV inhibitors block processing and export of gametocyte effector proteins and inhibit development of stage II-V gametocytes. Gametocytogenesis in the presence of sublethal inhibitor concentrations results in stage V gametocytes that fail to infect mosquitoes. Therefore, PMV primes gametocyte effectors for export, which is essential for the development and fitness of gametocytes for transmission to mosquitoes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Protozoan Proteins
/
Aspartic Acid Endopeptidases
/
Malaria, Falciparum
/
Enzyme Inhibitors
/
Gametogenesis
/
Culicidae
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2019
Document type:
Article
Affiliation country:
Australia
Country of publication:
United States