Involvement of autophagy in differentiation and response to nutritional stress in the Protozoan parasite Trypanosoma cruzi.

VANINA E. ALVAREZ; GREGOR KOSEC; VITO TURK; JUAN J. CAZZULO; BORIS TURK

Huerta Grande, Córdoba, Argentina.

Otro; XXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP 2006).; 2006

Sociedad Argentina de Protozoología.

Trypanosoma cruzi, the protozoan parasite causing Chagas Disease, has a complex life cycle, involving an insect vector and a mammal, and four major developmental stages. It is possible that the differentiation steps, and the response to the nutritional stress suffered inside the vector, may involve autophagy.    This process has not been studied in detail in the parasite, and nothing was known about their molecular mechanism.  Data from the recently completed Genome Project suggest that a pathway involving proteins homologous to yeast Atg4 (autophagin) and Atg8 may be operative in T. cruzi.   Two Atg4 and two Atg8 homologues have been cloned and expressed in Escherichia coli. Both T. cruzi autophagins are cysteine peptidases able to process the Atg8 homologues at the conserved Gly residue. Both autophagins were shown to be able to complement the autophagy defect observed in a yeast strain defective in Atg4.   In addition, at least one of the two T. cruzi Atg8 homologues (Atg8.1) was able to complement Atg8 deficiency in yeast. Antibodies against Atg8.1 were used to demonstrate that it is a suitable autophagosomal marker during nutritional stress in T. cruzi.  Using this tool, autophagy was demonstrated to take place during differentiation of epimastigotes to the infective stage, the metacyclic trypomastigote, which takes place at the rear end of the insect vector gut.  If autophagy is also involved in parasite remodeling inside the infected mammal, inhibition of this process might represent a novel strategy in searching for new antiparasitic drugs.