Format

Send to

Choose Destination
J Clin Invest. 2012 Jun;122(6):2301-5. doi: 10.1172/JCI61822. Epub 2012 May 8.

Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors.

Author information

1
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington 98195-6423, USA.

Abstract

Effective control and eradication of malaria will require new tools to prevent transmission. Current antimalarial therapies targeting the asexual stage of Plasmodium do not prevent transmission of circulating gametocytes from infected humans to mosquitoes. Here, we describe a new class of transmission-blocking compounds, bumped kinase inhibitors (BKIs), which inhibit microgametocyte exflagellation. Oocyst formation and sporozoite production, necessary for transmission to mammals, were inhibited in mosquitoes fed on either BKI-1-treated human blood or mice treated with BKI-1. BKIs are hypothesized to act via inhibition of Plasmodium calcium-dependent protein kinase 4 and predicted to have little activity against mammalian kinases. Our data show that BKIs do not inhibit proliferation of mammalian cell lines and are well tolerated in mice. Used in combination with drugs active against asexual stages of Plasmodium, BKIs could prove an important tool for malaria control and eradication.

PMID:
22565309
PMCID:
PMC3366411
DOI:
10.1172/JCI61822
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center