Biological function and molecular mapping of M antigen in yeast phase of Histoplasma capsulatum

Allan Jefferson Guimaräes, Andrew John Hamilton, Herbert Leonel de M. Guedes, Joshua Daniel Nosanchuk, Rosely Maria Zancopé-Oliveira

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30 Scopus citations

Abstract

Histoplasmosis, due to the intracellular fungus Histoplasma capsulatum, can be diagnosed by demonstrating the presence of antibodies specific to the immunodominant M antigen. However, the role of this protein in the pathogenesis of histoplasmosis has not been elucidated. We sought to structurally and immunologically characterize the protein, determine yeast cell surface expression, and confirm catalase activity. A 3D-rendering of the M antigen by homology modeling revealed that the structures and domains closely resemble characterized fungal catalases. We generated monoclonal antibodies (mAbs) to the protein and determined that the M antigen is present on the yeast cell surface and in cell wall/ cell membrane preparations. Similarly, we found that the majority of catalase activity was in extracts containing fungal surface antigens and that the M antigen is not significantly secreted by live yeast cells. The mAbs also identified unique epitopes on the M antigen. The localization of the M antigen to the cell surface of H. capsulatum yeast and the characterization of the protein's major epitopes have important implications since it demonstrates that although the protein may participate in protecting the fungus against oxidative stress it is also accessible to host immune cells and antibody.

Original languageEnglish (US)
Article numbere3449
JournalPloS one
Volume3
Issue number10
DOIs
StatePublished - Oct 17 2008

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Guimaräes, A. J., Hamilton, A. J., Guedes, H. L. D. M., Nosanchuk, J. D., & Zancopé-Oliveira, R. M. (2008). Biological function and molecular mapping of M antigen in yeast phase of Histoplasma capsulatum. PloS one, 3(10), [e3449]. https://doi.org/10.1371/journal.pone.0003449