Niche-Specific Activation of the Oxidative Stress Response by the Pathogenic Fungus Candida albicans

Brice Patrick Enjalbert, Donna Margaret MacCallum, Frank Christopher Odds, Alistair James Petersen Brown

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Candida albicans is a major opportunistic pathogen of humans. The pathogenicity of this fungus depends upon its ability to deal effectively with the host defenses and, in particular, the oxidative burst of phagocytic cells. We have explored the activation of the oxidative stress response in C. albicans in ex vivo infection models and during systemic infection of a mammalian host. We have generated C. albicans strains that contain specific green fluorescent protein (GFP) promoter fusions and hence act as biosensors of environmental oxidative stress at the single-cell level. Having confirmed that CTA1-, TRX1-, and TTR1/GRX2-GFP reporters respond specifically to oxidative stress, and not to heat shock, nitrosative, or osmotic stresses, we used these reporters to show that individual C. albicans cells activate an oxidative stress response following phagocytosis by neutrophils, but not by macrophages. Significantly, only a small proportion of C. albicans cells (about 4%) activated an oxidative stress response during systemic infection of the mouse kidney. The response of these cells was generally equivalent to exposure to 0.4 mM hydrogen peroxide in vitro. We conclude that most C. albicans cells are exposed to an oxidative stress when they come into contact with neutrophils in the bloodstream of the host but that oxidative killing is no longer a significant threat once an infection has been established in the kidney.
Original languageEnglish
Pages (from-to)2143-2151
Number of pages9
JournalInfection and Immunity
Volume75
Issue number5
Early online date5 Mar 2007
DOIs
Publication statusPublished - May 2007

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Keywords

  • animals
  • candida albicans
  • candidiasis
  • cell line
  • female
  • fungal proteins
  • gene expression regulation, fungal
  • green fluorescent proteins
  • humans
  • kidney
  • macrophages
  • mice
  • mice, inbred BALB C
  • neutrophils
  • oxidative stress
  • phagocytosis
  • recombinant fusion proteins
  • virulence

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