Inositol phosphorylceramide synthase null Leishmania are viable and virulent in animal infections where salvage of host sphingomyelin predominates

F Matthew Kuhlmann, Washington University School of Medicine in St. Louis
Phillip N Key, Washington University School of Medicine in St. Louis
Suzanne M Hickerson, Washington University School of Medicine in St. Louis
John Turk, Washington University School of Medicine in St. Louis
Fong-Fu Hsu, Washington University School of Medicine in St. Louis
Stephen M Beverley, Washington University School of Medicine in St. Louis

Abstract

Many pathogens synthesize inositol phosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate. The divergence between IPC synthase and mammalian SL synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lack de novo SL synthesis (Δspt2