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Antimicrobial Agents and Chemotherapy, August 2007, p. 2905-2910, Vol. 51, No. 8
0066-4804/07/$08.00+0     doi:10.1128/AAC.00022-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SB-431542, a Transforming Growth Factor ß Inhibitor, Impairs Trypanosoma cruzi Infection in Cardiomyocytes and Parasite Cycle Completion{triangledown}

Mariana C. Waghabi,1,2 Michelle Keramidas,3,4,5 Claudia M. Calvet,6 Marcos Meuser,2 Maria de Nazaré C. Soeiro,2 Leila Mendonça-Lima,1 Tania C. Araújo-Jorge,2 Jean-Jacques Feige,3,4,5 and Sabine Bailly3,4,5*

Laboratorio de Genômica Funcional e Bioinformática, Departamento de Bioquímica e Biologia Molecular,1 Laboratorio de Biologia Celular,2 Laboratorio de Ultraestrutura Celular, Departamento de Ultraestrutura e Biologia Celular, Instituto Oswaldo Cruz, Av. Brasil 4365, Rio de Janeiro RJ 21045, Brazil,6 INSERM (Institut National de la Santé et de la Recherche Médicale), U878, 17 rue des Martyrs, 38054 Grenoble,3 CEA (Commissariat à l'Energie Atomique), iRTSV (Institut de Recherches en Technologies et Sciences pour le Vivant)/APV (Angiogenèse et Physiopathologie Vasculaire),4 Université Joseph Fourier, Grenoble, France5

Received 8 January 2007/ Returned for modification 6 March 2007/ Accepted 20 May 2007

The antiinflammatory cytokine transforming growth factor ß (TGF-ß) plays an important role in Chagas disease, a parasitic infection caused by the protozoan Trypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of the TGF-ß type I receptor (ALK5), inhibits T. cruzi-induced activation of the TGF-ß pathway in epithelial cells and in cardiomyocytes. Further, we demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion by T. cruzi. Finally, SB-431542 treatment significantly reduces the number of parasites per infected cell and trypomastigote differentiation and release. Taken together, these data further confirm the major role of the TGF-ß signaling pathway in both T. cruzi infection and T. cruzi cell cycle completion. Our present data demonstrate that small inhibitors of the TGF-ß signaling pathway might be potential pharmacological tools for the treatment of Chagas disease.

* Corresponding author. Mailing address: INSERM U878, 17, Rue des Martyrs, 38054 Grenoble Cedex 9, France. Phone: (33) 438 789 214. Fax: (33) 438 785 058. E-mail: sbailly{at}cea.fr

{triangledown} Published ahead of print on 25 May 2007.

Antimicrobial Agents and Chemotherapy, August 2007, p. 2905-2910, Vol. 51, No. 8
0066-4804/07/$08.00+0     doi:10.1128/AAC.00022-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Waghabi, M. C., de Souza, E. M., de Oliveira, G. M., Keramidas, M., Feige, J.-J., Araujo-Jorge, T. C., Bailly, S. (2009). Pharmacological Inhibition of Transforming Growth Factor {beta} Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease. Antimicrob. Agents Chemother. 53: 4694-4701 [Abstract] [Full Text]  


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