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Cell differentiation and infectivity of Leishmania mexicana are inhibited in a strain resistant to an ABC-transporter blocker

Published online by Cambridge University Press:  13 May 2004

N. SILVA ,
N. CAMACHO ,
K. FIGARELLA  and
A. PONTE-SUCRE
N. SILVA
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
N. CAMACHO
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
K. FIGARELLA
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
A. PONTE-SUCRE
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela Present address, Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Röntgenring 11, D-97070 Würzburg, Germany. Tel: +49 931 31 2627. Fax: +49 931 31 2578. E-mail: aiponte@reacciun.ve
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Abstract

We analysed whether markers of cell differentiation and infectivity differed when compared to the parental sensitive strain [NR(Gs)] in an in vitro selected Leishmania strain [NR(Gr)] resistant to Glibenclamide®, an ATP-binding-cassette (ABC)-transporter blocker. The data show that the cell body area was larger in NR(Gr) compared to NR(Gs) and that functional characters associated with an infective metacyclic phenotype, such as resistance to the lytic effect of the alternative complement pathway and expression of the Meta-1 protein, were reduced. The infectivity of NR(Gr) to J774.1 macrophages was also significantly reduced. These results suggest that resistance in Leishmania against Glibenclamide®, a general blocker of P-glycoproteins, could produce functional modifications that may be relevant for Leishmania differentiation, infectivity and survival.

Keywords

cell differentiationcell survivaldrug resistanceinfectivityLeishmania mexicana
Type
Research Article
Information
Parasitology , Volume 128 , Issue 6 , June 2004 , pp. 629 - 634
Copyright
2004 Cambridge University Press

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