Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Animals

Anopheles/*parasitology

Communicable Disease Control/methods

Focal Adhesion Kinase 2/*antagonists & inhibitors/metabolism

Humans

*Malaria

Falciparum/enzymology/prevention & control/transmission

Mice

Plasmodium berghei/*enzymology

Plasmodium falciparum/*enzymology

Protein Kinase Inhibitors/*pharmacology

Protozoan Proteins/*antagonists & inhibitors

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)