Discovery of essential kinetoplastid-insect adhesion proteins and their function inLeishmania-sand fly interactions

Abstract

Leishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide 1 . Leishmania has a complex life cycle with multiple developmental forms, as it cycles between a sand fly vector and a mammalian host; understanding their life cycle is critical to understanding disease spread 2 . One of the key life cycle stages is the haptomonad form, which is attached to the insect through its flagellum. This adhesion, which is conserved across kinetoplastid parasites, is implicated to have an important function within their life cycles and hence on disease transmission 3–5 . Here, we discovered kinetoplastid-insect adhesion proteins (KIAPs), which are localised in the attached haptomonad flagellum. Deletion of these KIAPs impaired cell adhesion in vitro and prevented Leishmania from colonising the stomodeal valve in the sand fly, without affecting cell growth. This result will provide important insights for a comprehensive understanding of the Leishmania life cycle.