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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
08:48

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis

Published on: March 19, 2019

Multiple functions of DOA1 in Candida albicans

Donika Kunze1, Donna MacCallum2, Frank C Odds2

  • 1Robert Koch-Institut, Nordufer 20, D-13353, Berlin, Germany.

Microbiology (Reading, England)
|March 24, 2007
PubMed

Insights

The Candida albicans DOA1 gene regulates ubiquitin-dependent protein degradation and morphology. Mutants show altered growth, enzyme secretion, and sensitivity, highlighting its crucial role in fungal cell processes.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Fungal Pathogenesis

Background:

  • The human-pathogenic fungus Candida albicans requires regulation of virulence factors.
  • Ubiquitin-dependent protein degradation is a key cellular process.
  • Orthologs of DOA1 in other organisms, like Saccharomyces cerevisiae, are involved in protein degradation.

Purpose of the Study:

  • To identify and characterize regulators of virulence in Candida albicans.
  • To investigate the function of a novel gene, CaDOA1, similar to known protein degradation and signaling proteins.
  • To explore the role of CaDOA1 in Candida albicans cellular processes and morphology.

Main Methods:

  • Gene identification and sequence analysis.
  • Gene disruption and phenotypic analysis of mutants (colony morphology, temperature sensitivity, enzyme secretion, compound sensitivity).
  • Transcriptional profiling of gene-disrupted mutants.

Main Results:

  • CaDOA1, containing WD-repeats and a functional mellitin-like sequence, is expressed under all conditions.
  • Disruption of CaDOA1 leads to altered colony morphology, temperature sensitivity, reduced enzyme secretion, and hypersensitivity to various compounds.
  • Deltadoa1 mutants exhibit a striking switch to filamentous growth (pseudohyphae and true hyphae) under yeast-promoting conditions.
  • Upregulation of ubiquitin-mediated proteolysis genes (e.g., CDC48, UBI4) was observed in Deltadoa1 mutants.
  • CaDOA1 shares functions with its S. cerevisiae orthologue but also possesses unique roles in C. albicans.

Conclusions:

  • CaDOA1 is involved in ubiquitin-mediated proteolysis in Candida albicans.
  • CaDOA1 plays a significant role in regulating fungal morphology, including the yeast-to-hyphal transition.
  • Ubiquitin-mediated proteolysis is a critical pathway for controlling morphology in Candida albicans.
  • CaDOA1 represents a potential target for understanding and manipulating C. albicans virulence.

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