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Candida tropicalis PMT2 Is a Dispensable Gene for Viability but Required for Proper Interaction with the Host

Marco J Hernández-Chávez1, Iván Martínez-Duncker2, Diana M Clavijo-Giraldo1

  • 1Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P., Guanajuato 36050, GTO, Mexico.

Journal of Fungi (Basel, Switzerland)
|July 26, 2024
PubMed

Insights

O-linked mannans in Candida tropicalis are crucial for cell wall integrity, biofilm formation, and host interaction. Their absence attenuates virulence, highlighting their role in fungal pathogenesis.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Candidemia, caused by Candida species, presents significant mortality.
  • Candida tropicalis is a relevant pathogen, yet its biology, especially cell wall composition, is less understood than Candida albicans.
  • O-linked mannans are known cell wall components, but their specific roles in C. tropicalis require further investigation.

Purpose of the Study:

  • To investigate the function of O-linked mannans in Candida tropicalis by generating and characterizing a pmt2∆ null mutant.
  • To elucidate the contribution of O-linked mannans to C. tropicalis cell wall structure, virulence, and host-pathogen interactions.

Main Methods:

  • Generation of a pmt2∆ null mutant in Candida tropicalis.
  • Phenotypic characterization including filamentation, cell wall integrity, biofilm formation, protein secretion, and adhesion assays.
  • In vitro interaction studies with human innate immune cells (macrophages).
  • In vivo virulence assessment using Galleria mellonella larvae model.

Main Results:

  • The C. tropicalis pmt2∆ null mutant was viable, unlike in C. albicans where the gene is essential.
  • O-linked mannans were found to be essential for filamentation, cell wall integrity, biofilm formation, protein secretion, and adhesion to fibronectin and collagens.
  • The mutant showed reduced cytokine production but increased phagocytosis by macrophages.
  • The null mutant exhibited attenuated virulence in the Galleria mellonella model.

Conclusions:

  • O-linked mannans are critical for multiple aspects of Candida tropicalis biology, including structural integrity and virulence.
  • These findings provide new insights into the pathogenesis of C. tropicalis infections.
  • Targeting O-linked mannosylation pathways could be a potential strategy for antifungal therapies.
Keywords:
O-linked mannanadhesionfungal cell wallglycosylationinnate immune sensingphagocytosisvirulenceβ-1,3-glucan

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