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Src and PI3 K inhibitors affect the virulence factors of Entamoeba histolytica

Published online by Cambridge University Press:  12 October 2012

L. LÓPEZ-CONTRERAS
Affiliation:
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies, Av. IPN 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico
V. I. HERNÁNDEZ-RAMÍREZ
Affiliation:
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies, Av. IPN 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico
Y. FLORES-GARCÍA
Affiliation:
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies, Av. IPN 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico
B. CHÁVEZ-MUNGUÍA
Affiliation:
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies, Av. IPN 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico
P. TALAMÁS-ROHANA*
Affiliation:
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies, Av. IPN 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico
*
*Corresponding author: E-mail: [email protected]

Summary

Protein kinases (PKs) of parasitic protozoa are being evaluated as drug targets. A large number of protein kinases within the protein kinome of Entamoeba histolytica strongly suggest that protein phosphorylation is a key component of pathogenesis regulation by this parasite. PI3 K and Src are kinases previously described in this parasite, but their role is poorly understood. Here, the effect of Src-1-inhibitor and PI3 K inhibitor (Wortmannin) on the virulence factors of E. histolytica was evaluated. Results show that both inhibitors affect the actin cytoskeleton and the amoebic movement. Also, the proteolytic activity is diminished by Wortmannin, but not by Src-inhibitor-1; however, the phagocytic capacity is diminished by Wortmannin and Src-1-inhibitor. Finally, we found that the virulence in vivo of E. histolytica is affected by Wortmannin but not by Src-1-inhibitor. This study opens the way for the design of anti-amoebic drugs based on kinase inhibition.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2012

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