Identification of Components of the SUMOylation Machinery in Candida glabrata: ROLE OF THE DESUMOYLATION PEPTIDASE CgUlp2 IN VIRULENCE

J Biol Chem. 2016 Sep 9;291(37):19573-89. doi: 10.1074/jbc.M115.706044. Epub 2016 Jul 5.

Abstract

Regulation of protein function by reversible post-translational modification, SUMOylation, is widely conserved in the eukaryotic kingdom. SUMOylation is essential for cell growth, division, and adaptation to stress in most organisms, including fungi. As these are key factors in determination of fungal virulence, in this study, we have investigated the importance of SUMOylation in the human pathogen, Candida glabrata We identified the enzymes involved in small ubiquitin-like modifier conjugation and show that there is strong conservation between Saccharomyces cerevisiae and C. glabrata We demonstrate that SUMOylation is an essential process and that adaptation to stress involves changes in global SUMOylation in C. glabrata Importantly, loss of the deSUMOylating enzyme CgUlp2 leads to highly reduced small ubiquitin-like modifier protein levels, and impaired growth, sensitivity to multiple stress conditions, reduced adherence to epithelial cells, and poor colonization of specific tissues in mice. Our study thus demonstrates a key role for protein SUMOylation in the life cycle and pathobiology of C. glabrata.

Keywords: C. glabrata; Epa adhesins; SUMO ligase; SUMO peptidase; adhesion; biofilm; fungal pathogenesis; microbial pathogenesis; small ubiquitin-like modifier (SUMO); sumoylation.

MeSH terms

  • Animals
  • Candida glabrata / enzymology*
  • Candida glabrata / genetics
  • Candida glabrata / pathogenicity*
  • Candidiasis / enzymology*
  • Candidiasis / genetics
  • Candidiasis / pathology
  • Cell Line, Tumor
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Sumoylation*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • Fungal Proteins
  • Virulence Factors
  • Endopeptidases