Candida parapsilosis fat storage-inducing transmembrane (FIT) protein 2 regulates lipid droplet formation and impacts virulence

Long N. Nguyen, Zsuzsanna Hamari, Bert Kadereit, David Trofa, Mariangela Agovino, Luis R. Martinez, Attila Gacser, David L. Silver, Joshua D. Nosanchuk

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Neutral lipid storage in lipid droplets (LDs) is a conserved process across diverse species. Although significant attention has focused on LDs in the biology of obesity, diabetes, and atherosclerosis, there is limited information on the role of LDs in pathogenic fungi. We have disrupted the Fat storage-Inducing Transmembrane (FIT) protein 2 genes of the emerging pathogenic fungus Candida parapsilosis and demonstrated that LD formation is significantly reduced in the mutant cells. Disruption of FIT2 genes also reduced accumulation of triacylglycerols. The production of other lipids such as phospholipids and steryl esters were also affected in the mutant strain. Inhibition of de novo fatty acid biosynthesis by triclosan in the FIT2 disruptants reduced fungal growth in rich medium YPD, indicating that TAGs or fatty acids from the LDs could be important for cell proliferation. FIT2 disruption was associated with enhanced sensitivity to oxidative stress. Furthermore, we showed that FIT2 deletion yeast cells were significantly attenuated in murine infection models, suggesting an involvement of LDs in the pathobiology of the fungus.

Original languageEnglish (US)
Pages (from-to)663-672
Number of pages10
JournalMicrobes and Infection
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2011

Keywords

  • Candida
  • Fatty acid synthesis
  • Lipid droplet
  • Pathogenesis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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