Endocytosis and Sphingolipid Scavenging inLeishmania mexicanaAmastigotes

Abstract

Leishmaniaspecies are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example,Leishmaniaspecies utilise host sphingolipid for synthesis of complex sphingolipid. In this studyL. mexicanaendocytosis was shown to be significantly upregulated in amastigotes, indicating that sphingolipid scavenging may be enhanced. However, inhibition of host sphingolipid biosynthesis had no significant effect on amastigote proliferation within a macrophage cell line. In addition, infection itself did not directly influence host biosynthesis. Notably, in contrast toL. major,L. mexicanaamastigotes are indicated to possess a complete biosynthetic pathway suggesting that scavenged sphingolipids may be nonessential for proliferation. This suggested that Old and New World species differ in their interactions with the macrophage host. This will need to be considered when targeting theLeishmaniasphingolipid biosynthetic pathway with novel therapeutics.