Effect of inhibitor of sphingolipid synthesis on Leishmania (Viannia) braziliensis cytokinesis

Abstract

Leishmania (Viannia) braziliensis is a parasite widely distributed in Brazil and the causative agent of cutaneous leishmaniasis and occasional mucosal or mucocutaneous disease. The role of L. braziliensis sphingolipids was analyzed using myriocin, an inhibitor of serine palmitoyltransferase. Myriocin 5 μM significantly reduced synthesis of inositol phosphorylceramide (IPC), as quantified by high performance thin layer chromatography and electrospray ionization mass spectrometry. Myriocin treated promastigotes displayed a variety of aberrant cell phenotypes. The percentage of cells with one nucleus and one kinetoplast (1N1K), decreased from 89% (control) to 27% or 3% following treatment with 1 μM or 5 μM myriocin, respectively. High percentage of myriocin treated parasites exhibited large atypical cells presenting three or more nuclei (32% and 89% for 1 μM or 5 μM myriocin, respectively). It is noteworthy that addition of 2 μM 3‐ketodihidrosphingosine, a long‐chain base precursor of ceramide, restored IPC synthesis and parasite morphology. When L. braziliensis treated with 1 μM myriocin were analyzed by transmission electron microscopy it was observed 4N parasites, possibly as a result from an incomplete cytokinesis. Our findings indicate that sphingolipids are essential for completion of cytokinesis and may play a major role in L. braziliensis cell proliferation. Supported by FAPESP, CNPq, CAPES.