Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors

Kayode K. Ojo, Claudia Pfander, Natascha R. Mueller, Charlotte Burstroem, Eric T. Larson, Cassie M. Bryan, Anna M W Fox, Molly C. Reid, Steven Johnson, Ryan C. Murphy, Mark Kennedy, Henning Mann, David J. Leibly, Stephen N. Hewitt, Christophe L M J Verlinde, Stefan Kappe, Ethan A. Merritt, Dustin J. Maly, Oliver Billker, Wesley C. Van Voorhis

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2301-2305
Number of pages5
JournalJournal of Clinical Investigation
Volume122
Issue number6
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

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Culicidae
Malaria
Phosphotransferases
Plasmodium
Sporozoites
Oocysts
Antimalarials
Drug Combinations
Mammals
Cell Line

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ojo, K. K., Pfander, C., Mueller, N. R., Burstroem, C., Larson, E. T., Bryan, C. M., ... Van Voorhis, W. C. (2012). Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. Journal of Clinical Investigation, 122(6), 2301-2305. https://doi.org/10.1172/JCI61822

Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. / Ojo, Kayode K.; Pfander, Claudia; Mueller, Natascha R.; Burstroem, Charlotte; Larson, Eric T.; Bryan, Cassie M.; Fox, Anna M W; Reid, Molly C.; Johnson, Steven; Murphy, Ryan C.; Kennedy, Mark; Mann, Henning; Leibly, David J.; Hewitt, Stephen N.; Verlinde, Christophe L M J; Kappe, Stefan; Merritt, Ethan A.; Maly, Dustin J.; Billker, Oliver; Van Voorhis, Wesley C.

In: Journal of Clinical Investigation, Vol. 122, No. 6, 01.06.2012, p. 2301-2305.

Research output: Contribution to journalArticle

Ojo, KK, Pfander, C, Mueller, NR, Burstroem, C, Larson, ET, Bryan, CM, Fox, AMW, Reid, MC, Johnson, S, Murphy, RC, Kennedy, M, Mann, H, Leibly, DJ, Hewitt, SN, Verlinde, CLMJ, Kappe, S, Merritt, EA, Maly, DJ, Billker, O & Van Voorhis, WC 2012, 'Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors', Journal of Clinical Investigation, vol. 122, no. 6, pp. 2301-2305. https://doi.org/10.1172/JCI61822
Ojo KK, Pfander C, Mueller NR, Burstroem C, Larson ET, Bryan CM et al. Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. Journal of Clinical Investigation. 2012 Jun 1;122(6):2301-2305. https://doi.org/10.1172/JCI61822
Ojo, Kayode K. ; Pfander, Claudia ; Mueller, Natascha R. ; Burstroem, Charlotte ; Larson, Eric T. ; Bryan, Cassie M. ; Fox, Anna M W ; Reid, Molly C. ; Johnson, Steven ; Murphy, Ryan C. ; Kennedy, Mark ; Mann, Henning ; Leibly, David J. ; Hewitt, Stephen N. ; Verlinde, Christophe L M J ; Kappe, Stefan ; Merritt, Ethan A. ; Maly, Dustin J. ; Billker, Oliver ; Van Voorhis, Wesley C. / Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 6. pp. 2301-2305.
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