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Role of protein phosphomannosylation in the Candida tropicalis-macrophage interaction

Marco J Hernández-Chávez1, Bernardo Franco1, Diana M Clavijo-Giraldo1

  • 1Departamento de Biología, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P. 36050, Guanajuato, Gto., México.

FEMS Yeast Research
|May 3, 2018
PubMed

Insights

Candida tropicalis cell wall phosphomannans are crucial for phagocytosis by immune cells. Disrupting the MNN4 gene reduces phosphomannans, attenuating virulence in insect models.

Area of Science:

  • Mycology
  • Immunology
  • Molecular Biology

Background:

  • Candida tropicalis is an opportunistic fungal pathogen causing mucosal and systemic infections.
  • Cell wall mannoproteins, including phosphomannans, are key in host-fungal interactions.
  • MNN4 regulates phosphomannan synthesis in Candida albicans.

Purpose of the Study:

  • To investigate the presence and role of phosphomannans in Candida tropicalis.
  • To identify and characterize a functional ortholog of CaMNN4 in C. tropicalis.
  • To determine the impact of phosphomannan depletion on C. tropicalis virulence and host cell interactions.

Main Methods:

  • Identification and gene disruption of a C. tropicalis MNN4 ortholog.
  • Analysis of cell wall phosphomannan content.
  • Assessment of cytokine production by human mononuclear cells.
  • Virulence studies in an insect model of candidiasis.
  • Investigation of C. tropicalis-macrophage interactions.

Main Results:

  • C. tropicalis displays cell surface phosphomannans, with variable amounts across strains.
  • A functional C. tropicalis MNN4 ortholog was identified; its disruption depleted phosphomannans.
  • The mnn4Δ mutant showed no defects in cytokine induction but had attenuated virulence in insects.
  • Cell wall phosphomannan presence was critical for C. tropicalis phagocytosis by macrophages.

Conclusions:

  • Phosphomannans play a significant role in C. tropicalis cell wall structure and host interactions.
  • The C. tropicalis MNN4 gene is essential for phosphomannan synthesis and fungal phagocytosis.
  • Phosphomannans have a differential role in C. albicans versus C. tropicalis phagocytosis by host cells.

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