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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

Candida albicans RFX2 encodes a DNA binding protein involved in DNA damage responses, morphogenesis, and virulence

Binghua Hao1, Cornelius J Clancy, Shaoji Cheng

  • 1Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15203, USA.

Eukaryotic Cell
|March 3, 2009
PubMed

Insights

The study renames Candida albicans orf19.4590 to RFX2. This gene regulates DNA damage responses, morphogenesis, and virulence, impacting candidiasis progression.

Area of Science:

  • Mycology
  • Molecular Biology
  • Genetics

Background:

  • Candida albicans orf19.4590, renamed RFX2, encodes a protein reactive with antibodies in candidiasis patients.
  • Functional redundancy between C. albicans RFX2 and Saccharomyces cerevisiae RFX1 was previously suggested.

Purpose of the Study:

  • To investigate the function of C. albicans RFX2 in DNA damage response, morphogenesis, and virulence.
  • To characterize the phenotype of a C. albicans rfx2 null mutant.

Main Methods:

  • Complementation of S. cerevisiae rfx1 mutant with C. albicans RFX2.
  • Analysis of gene expression (RAD6, DDR48, HWP1, ALS3, HYR1, ECE1, CEK1) in C. albicans rfx2 null mutant.
  • Phenotypic characterization including UV, heat, and ethanol resistance, filamentation, adherence, invasion, and murine infection models (hematogenously disseminated and oropharyngeal candidiasis).

Main Results:

  • C. albicans RFX2 partially restored UV susceptibility and repressed DNA damage response genes in S. cerevisiae rfx1 mutant.
  • The C. albicans rfx2 null mutant showed derepressed DNA damage and UV-induced genes (RAD6, DDR48) and increased resistance to UV, heat, and ethanol.
  • The mutant exhibited hyperfilamentation, constitutive expression of hypha-specific genes, increased invasion and adherence, delayed mortality in disseminated candidiasis, and reduced tissue burden in oropharyngeal candidiasis.

Conclusions:

  • C. albicans Rfx2p plays a crucial role in regulating DNA damage responses.
  • Rfx2p influences C. albicans morphogenesis, including filamentation.
  • C. albicans RFX2 is a significant virulence factor affecting host-pathogen interactions and disease progression.

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