Blocking autophagy to prevent parasite differentiation: a possible new strategy for fighting parasitic infections?
The genome of Trypanosoma cruzi was surveyed for autophagy-related genes. We have identified all the essential genes except for the Atg12 conjugation system and demonstrated functionality of the putative ATG4 and ATG8 homologs. TcAtg4.1 was primarily involved in the proteolytic processing of TcAtg8.1, the ATG8-homolog that was found to be localized to autophagosomal membranes during starvation. Autophagy was also found to be strongly upregulated during differentiation between developmental stages, a process that is essential for the propagation of the parasite. Based on our work, new strategies for treatment of Chagas disease, a chronic debilitating condition still without suitable chemotherapy, can be envisioned.
Alvarez
Vanina E
VE
Instituto de Investigaciones Biotecnologicas (IIB/INTECH, UNSAM/CONICET), Buenos Aires, Argentina.
Kosec
Gregor
G
Sant Anna
Celso
C
Turk
Vito
V
Cazzulo
Juan J
JJ
Turk
Boris
B
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology*; D017125:Genes, Protozoan; D006790:Host-Parasite Interactions; D006801:Humans; D007303:Insect Vectors / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000235:genetics / Q000502:physiology*
D015800:Protozoan Proteins