Overexpression of a single Leishmania major gene enhances parasite infectivity in vivo and in vitro

Mol Microbiol. 2010 Jun 1;76(5):1175-90. doi: 10.1111/j.1365-2958.2010.07130.x. Epub 2010 Mar 25.


We identified a Leishmania major-specific gene that can partly compensate for the loss of virulence observed for L. major HSP100 null mutants. The gene, encoding a 46 kD protein of unknown function and lineage, also enhances the virulence of wild type L. major upon overexpression. Surprisingly, the approximately sixfold overexpression of this protein also extends the host range of L. major to normally resistant C57BL/6 mice, causing persisting lesions in this strain, even while eliciting a strong cellular immune response. This enhanced virulence in vivo is mirrored in vitro by increased parasite burden inside bone marrow-derived macrophages. The localization of the protein in the macrophage cytoplasm suggests that it may modulate the macrophage effector mechanisms. In summary, our data show that even minor changes of gene expression in L. major may alter the outcome of an infection, regardless of the host's genetic predisposition.

MeSH terms

  • Animals
  • Cytokines / immunology
  • Endopeptidase Clp
  • Female
  • Gene Expression Regulation*
  • Genetic Complementation Test
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Leishmania major / cytology
  • Leishmania major / genetics*
  • Leishmania major / immunology
  • Leishmania major / pathogenicity*
  • Leishmaniasis, Cutaneous / genetics
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / parasitology
  • Macrophages / immunology
  • Macrophages / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Open Reading Frames
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism


  • Cytokines
  • Heat-Shock Proteins
  • Protozoan Proteins
  • Endopeptidase Clp
  • ClpB protein, Leishmania