Title: Leucinostatins prevent malaria transmission to mosquitoes.

By: Jun Li, Ph.D.

Associate Professor

Biological Sciences

Abstract

Malaria remains a significant disease. Anopheles mosquitoes transmit it. The lack of efficient malaria vaccines and the recent increase malaria cases urge innovative approaches to prevent malaria. Previously, we reported that the extract of Purpureocillium lilacinum, a common fungus from the soil, reduced Plasmodium falciparum oocysts in Anopheles gambiae midguts after mosquitoes contacted the treated surface before feeding.

We used liquid chromatography to fraction fungal crude extract and tract the active fraction using a contact-wise approach and standard membrane feeding assays. The purified small molecules were analyzed by precise mass spectrometry and tandom mass spectrometry. We isolated four active small molecules from P. lilacinum to be leucinostatin A, B, A2, and B2. Pre-exposure of leucinostatin A at a very low level to mosquitoes via contact significantly reduced the number of oocysts. The concentration that gave half-maximal response or inhibition (EC₅₀) via pre-exposure is 0.7 mg/m², similar to atovaquone and better than other known antimalarials. The inhibition of leucinostatin A against P. falciparum at the erythrocytic stage, gametogenesis, sporogonic development, and ookinetes are positive except sporogonic development, suggesting leucinostatins play functions during parasite invasion of new cells. These findings underscore the potential of leucinostatins for malaria transmission disruption at malaria endemic areas, where conventional approaches are highly needed.

Lunch will be provided.