CALMODULIN ANTAGONIST INHIBIT ECHINOCOCCUS GRANULOSUS: IMPLICATIONS FOR DRUG DESIGN

LAMENZA P., DENEGRI G., CUMINO A. C.

Mar del Plata, Argentina (17-20 November)

Congreso; XLIII Annual Meeting SAIB; 2007

Argentine Society for Biochemistry and Molecular Biology Research

Shape change is required for the invasion the same protozoans and these transitions morphology are drive by calcium-dependent signaling pathways. The presence of specific calcium storage compartments, calcium transport and different calcium-binding proteins are vital signal systems for these eukaryotes. On the other hand, broad spectrum antiparasitic agents altered Ca2+-dependent metabolism processes in the cells. In Echinococcus granulosus, the Ca2+ deposits, IP6 and proteins (EgCaBP) are very abundant in the calcareous corpuscles and in the cystic membranes but physiologic function is ignored. We found by RT-PCR that Echinococcus larvae contain calmodulin. Additionally, agents that affect both intracellular (BAPTA) and extracellular calcium (EGTA, verapamil) homeostasis reduced the vitality of protoscoleces in a dose-dependent manner. Scanning electron and confocal microscopy were determined. The ID50 concentration were determined for CaM antagonists (W7), phenothiazines (TFP) and protein-kinase inhibitors and was demonstrate the deleterious effect on laminated layer of intact cysts. Protoscolex mortality was 100% after CaM antagonist incubation for 18 h. Further study of this process may identify novel mechanisms involved in the development of the cestode and may contribute to the design of novel strategies to control echinococcosis transmission.