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

Abstract

Leishmaniaspecies, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide1.Leishmaniahas 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 spread2. 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 transmission3–5. Here, we discovered kinetoplastid-insect adhesion proteins (KIAPs), which are localised in the attached haptomonad flagellum. Deletion of these KIAPs impaired cell adhesionin vitroand preventedLeishmaniafrom colonising the stomodeal valve in the sand fly, without affecting cell growth. This result will provide important insights for a comprehensive understanding of theLeishmanialife cycle.

A sticky situation: When trypanosomatids attach to insect tissues

“…Excitingly, 3 attachment plaque proteins have recently been described in L . mexicana [ 141 ]. These KIAPs (kinetoplast-insect adhesion proteins) localize to the attachment plaque membrane (KIAP1 and 3) or to the filaments (KIAP2) and are required for attachment both in vitro and in vivo.…”

“…In swimming promastigotes, KIAP2 is found primarily at the base of the flagellum where it exits the cell body, while KIAP1 and 3 localize diffusely. During initial adhesion, all 3 KIAPs accumulate at points of membrane deformation and stably associate with the attachment plaque during and after flagellar disassembly [ 141 ].…”