Vector competence of sand flies to Leishmania parasites and Toscana virus

Abstract

Phlebotomine sand flies transmit a range of human pathogens, including Leishmania parasites and viruses such as Toscana virus (TOSV). Recent studies have shown that Phlebotomus tobbi and P. sergenti, two species widespread in the Mediterranean and Middle East, are susceptible to TOSV and are likely natural vectors. In contrast, P. papatasi, a highly anthropophilic species found from the Mediterranean to India, appears resistant to TOSV infection. Leishmania development in sand flies involves several critical steps, including attachment to the midgut epithelium and the stomodeal valve (SV). These processes are mediated by both parasite- and vector-derived molecules.Attachment to the midgut is essential to prevent the parasites from being lost during defecation and is a critical determinant of vector competence. In species like P. papatasi, this attachment relies on interactions between parasite lipophosphogly can and vector galectins. In permissive species such as Lutzomyia longipalpis, mucin-based adhesion mechanisms predominate. In late-stage infections, Leishmania promastigotes attach to the SV, forming emidesmosome-like plaques and secreting promastigote secretory gel (PSG). PSG blocks the gut, impairs bloodmeal uptake, and promotes parasite transmission. These "blocked" flies struggle to feed and bite repeatedly, increasing the likelihood of transmission. Recent studies identified three flagellar proteins, Kinetoplastid-Insect Attachment Proteins (KIAPs), as essential for SV attachment. Knocking out these proteins disrupts plaque formation and PSG secretion. While the parasites can persist in the midgut, they fail to colonize the SV, suggesting KIAPs are crucial for PSG production and effective transmission.