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American Society for Microbiology, Infection and Immunity, 6(71), p. 3190-3195, 2003

DOI: 10.1128/iai.71.6.3190-3195.2003

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Expression of MultipleCPBGenes Encoding Cysteine Proteases Is Required forLeishmania mexicanaVirulence In Vivo

Journal article published in 2003 by Hubert Denise ORCID, Kathryn McNeil, Darren R. Brooks, James Alexander, Graham H. Coombs, Jeremy C. Mottram
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

ABSTRACT Leishmania mexicana mutants deficient in the multicopy CPB gene array have reduced virulence, demonstrated by poor lesion growth in BALB/c mice and induction of a protective Th1 response. Reinsertion of the amastigote-specific CPB2.8 or metacyclic stage-specific CPB2 gene into a CPB -deficient mutant L. mexicana failed to restore either a Th2 response or sustained virulence. However, reexpression of multiple CPB genes from a cosmid significantly restored virulence. This was characterized by increased lesion and parasite growth and the acquisition of a Th2 response, as determined by measuring interleukin-4 production and immunoglobulin G1 (IgG1) and IgE levels. These studies confirm that L. mexicana cysteine proteases are important virulence factors and provide an explanation for the presence in L. mexicana of a multicopy tandem array of CPB genes.