title: Effects of sterol biosynthesis inhibitors on endosymbiont-bearing trypanosomatids.
abstract: Some protozoa of the Trypanosomatidae family have a close relationship with an endosymbiotic bacterium. As the prokaryote envelope has a controversial origin, a sterol 24-methyltransferase inhibitor (20-piperidin-2-yl-5alpha-pregnan-3beta,20-diol; 22,26-azasterol) was used as a tool to investigate lipid biosynthetic pathways in Crithidia deanei, an endosymbiont-bearing trypanosomatid. Apart from antiproliferative effects, this drug induced ultrastructural alterations, consisting of myelin-like figures in the cytoplasm and endosymbiont envelope vesiculation. Concurrently, a dramatic reduction of 24-alkyl sterols was observed after 22,26-azasterol treatment, both in whole cell homogenates, as well as in isolated mitochondria. These effects were associated with changes of phospholipid composition, in particular a reduction of the phosphatidylcholine content and a concomitant increase in phosphatidylethanolamine levels. Lipid analyses of purified endosymbionts indicated a complete absence of sterols, and their phospholipid composition was different from that of mitochondria or whole protozoa, being similar to eubacteria closely associated with eukaryotes.
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Isabella Vieira
authors.initials: IV
authors.lastname: Palmié-Peixoto
authors.forename: Marcia Rosa
authors.initials: MR
authors.lastname: Rocha
authors.forename: Julio A
authors.initials: JA
authors.lastname: Urbina
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
authors.forename: Marcelo
authors.initials: M
authors.lastname: Einicker-Lamas
authors.forename: Maria Cristina Machado
authors.initials: MC
authors.lastname: Motta
mesh_terms: D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000187:drug effects*; D004083:Cholestanol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D013261:Sterols / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013559:Symbiosis; D014351:Trypanosomatina / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure
chemical_list: C103731:22,26-azasterol; D004791:Enzyme Inhibitors; D013261:Sterols; D004083:Cholestanol