Leishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide. 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. One of the key life cycle stages is the haptomonad form, which attaches to insect tissues through its flagellum. This adhesion, conserved across kinetoplastid parasites, is implicated in having an important function within their life cycles and hence in disease transmission. Here, we discover the kinetoplastid-insect adhesion proteins (KIAPs), which localise in the attached Leishmania flagellum. Deletion of these KIAPs impairs cell adhesion in vitro and prevents Leishmania from colonising the stomodeal valve in the sand fly, without affecting cell growth. Additionally, loss of parasite adhesion in the sand fly results in reduced physiological changes to the fly, with no observable damage of the stomodeal valve and reduced midgut swelling. These results provide important insights into a comprehensive understanding of the Leishmania life cycle, which will be critical for developing transmission-blocking strategies.

Department of Basic Biology School of Life Science SOKENDAI Okazaki Japan

Department of Biochemistry Central Oxford Structural Molecular Imaging Centre University of Oxford Oxford UK

Department of Biological and Medical Sciences Oxford Brookes University Oxford UK

Department of Genetics and Genome Biology University of Leicester Leicester UK

Department of Parasitology Faculty of Science Charles University Prague Czechia

Laboratory for Spatiotemporal Regulations National Institute for Basic Biology Okazaki Japan

Research Center of Mathematics for Social Creativity Research Institute for Electronic Science Hokkaido University Sapporo Japan

School of Life Sciences University of Nottingham Nottingham UK

Spatiotemporal Regulations Group Exploratory Research Center for Life and Living Systems Okazaki Japan

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