Open AccessExpression of MultipleCPBGenes Encoding Cysteine Proteases Is Required forLeishmania mexicanaVirulence In Vivo
Author(s) -
Hubert Denise,
Kathryn S. McNeil,
Darren R. Brooks,
James Alexander,
Graham H. Coombs,
Jeremy C. Mottram
Publication year - 2003
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.71.6.3190-3195.2003
Subject(s) - virulence , biology , leishmania mexicana , amastigote , proteases , mutant , gene , leishmania major , leishmania , microbiology and biotechnology , genetics , parasite hosting , biochemistry , world wide web , computer science , enzyme
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.