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 Previous Article

Infection and Immunity, January 2008, p. 443-451, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.00400-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Impairment of Infectivity and Immunoprotective Effect of a LYT1 Null Mutant of Trypanosoma cruzi{triangledown}

M. Paola Zago,1 Alejandra B. Barrio,1 Rubén M. Cardozo,1 Tomás Duffy,2 Alejandro G. Schijman,2 and Miguel A. Basombrío1*

Instituto de Patología Experimental (INSIBIO-CONICET), Universidad Nacional de Salta, Salta, Argentina,1 Laboratorio de Biología Molecular de la Enfermedad de Chagas (LabMECh)-Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET), Buenos Aires, Argentina2

Received 16 March 2007/ Returned for modification 20 April 2007/ Accepted 29 September 2007

Trypanosoma cruzi infection of host cells is a complex process in which many proteins participate but only a few of these proteins have been identified experimentally. One parasite factor likely to be involved is the protein product of LYT1, a single-copy gene cloned, sequenced, and characterized by Manning-Cela et al. (Infect. Immun. 69:3916-3923, 2001). This gene was potentially associated with infectivity, since the deletion of both LYT1 alleles in the CL Brenner strain (the wild type [WT]) resulted in a null mutant T. cruzi clone (L16) that shows an attenuated phenotype in cell culture models. The aim of this work was to characterize the infective behavior of L16 in the insect vector and murine models. The infection of adult Swiss mice with 103 trypomastigotes of both clones revealed a significant reduction in infective behavior of L16, as shown by direct parasitemia, spleen index, and quantitation of tissue parasite burden, suggesting the loss of virulence in the null mutant clone. Although L16 blood counts were almost undetectable, blood-based PCRs indicated the presence of latent and persistent infection during all of the study period and epimastigotes were reisolated from hemocultures until 12 months postinfection. Nevertheless, virulence was not restored in L16 by serial passages in mice, and reisolated parasites lacking the LYT1 gene and bearing the antibiotic resistance genes revealed the stability of the genetic manipulation. Histopathological studies showed a strong diminution in the muscle inflammatory response triggered by L16 compared to that triggered by the WT group, consistent with a lower tissue parasite load. A strong protection against a virulent challenge in both L16- and WT-infected mice was observed; however, the immunizing infection by the genetically modified parasite was highly attenuated.

* Corresponding author. Mailing address: Instituto de Patología Experimental (CONICET), Universidad Nacional de Salta, Calle Buenos Aires 177, 4400 Salta, Argentina. Phone and fax: 54 387 4255333. E-mail: basombri{at}unsa.edu.ar

{triangledown} Published ahead of print on 15 October 2007.

Editor: W. A. Petri, Jr.

Infection and Immunity, January 2008, p. 443-451, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.00400-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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