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Eukaryotic Cell, August 2003, p. 756-768, Vol. 2, No. 4
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.4.756-768.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Formation and Remodeling of Inositolphosphoceramide during Differentiation of Trypanosoma cruzi from Trypomastigote to Amastigote

Maria Laura Salto,1,2 Laura E. Bertello,2 Mauricio Vieira,1 Roberto Docampo,1 Silvia N. J. Moreno,1* and Rosa M. de Lederkremer2*

Laboratory of Molecular Parasitology, Department of Pathobiology and Center for Zoonoses Research, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802,1 CIHIDECAR, Departamento de Quimica Organica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 2, Ciudad Universitaria, 1428 Buenos Aires, Argentina2

Received 4 April 2003/ Accepted 3 June 2003

Differentiation of Trypanosoma cruzi trypomastigotes to amastigotes inside myoblasts or in vitro, at low extracellular pH, in the presence of [3H]palmitic acid or [3H]inositol revealed differential labeling of inositolphosphoceramide and phosphatidylinositol, suggesting that a remodeling process takes place in both lipids. Using 3H-labeled inositolphosphoceramide and phosphatidylinositol as substrates, we demonstrated the association of at least five enzymatic activities with the membranes of amastigotes and trypomastigotes. These included phospholipase A1, phospholipase A2, inositolphosphoceramide-fatty acid hydrolase, acyltransferase, and a phospholipase C releasing either ceramide or a glycerolipid from the inositolphospholipids. These enzymes may be acting in remodeling reactions leading to the anchor of mature glycoproteins or glycoinositolphospholipids and helping in the transformation of the plasma membrane, a necessary step in the differentiation of slender trypomastigotes to round amastigotes. Synthesis of inositolphosphoceramide and particularly of glycoinositolphospholipids was inhibited by aureobasidin A, a known inhibitor of fungal inositolphosphoceramide synthases. The antibiotic impaired the differentiation of trypomastigotes at acidic pH, as indicated by an increased appearance of intermediate forms and a decreased expression of the Ssp4 glycoprotein, a characteristic marker of amastigote forms. Aureobasidin A was also toxic to differentiating trypomastigotes at acidic pH but not to trypomastigotes maintained at neutral pH. Our data suggest that inositolphosphoceramide is implicated in T. cruzi differentiation and that its metabolism could provide important targets for the development of antiparasitic therapies.

* Corresponding author. Mailing address for Silvia N. J. Moreno: Laboratory of Molecular Parasitology, Department of Pathobiology and Center for Zoonoses Research, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802. Phone: (217) 333-2746. Fax: (217) 244-7421. E-mail: s-moreno{at}uiuc.edu Mailing address for Rosa M. de Lederkremer: CIHIDECAR, Departamento de Quimica Organica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 2, Ciudad Universitaria, 1428 Buenos Aires, Argentina. Phone: 5411 4576 3352. Fax: 5411 4576 3346. E-mail: lederk{at}qo.fcen.uba.ar.

Eukaryotic Cell, August 2003, p. 756-768, Vol. 2, No. 4
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.4.756-768.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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