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

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

Rosario, Santa Fe, Argentina.

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB 2006).; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.

Trypanosoma cruzi, the parasite causing Chagas Disease, has a complex life cycle, involving an insect vector and a mammal, and four major developmental stages. 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 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, and to complement the autophagy defect observed in a yeast strain defective in Atg4.   In addition, one of the two T. cruzi Atg8 homologues (Atg8.1) was able to complement Atg8 deficiency in yeast. Atg8.1 is a suitable autophagosomal marker during nutritional stress in T. cruzi, as shown with specific antibodies.  Using this tool, autophagy was demonstrated to take place during differentiation of epimastigotes to metacyclic trypomastigotes at the end of the insect vector gut.  If autophagy is also involved in parasite remodeling inside the mammal, its inhibition might represent a novel strategy in searching for new antiparasitic drugs.