Hsp90 is involved in apoptosis of Candida albicans by regulating the calcineurin-caspase apoptotic pathway

PLoS One. 2012;7(9):e45109. doi: 10.1371/journal.pone.0045109. Epub 2012 Sep 18.


Candida albicans is the most common human fungal pathogen. Recent evidence has revealed the occurrence of apoptosis in C. albicans that is inducible by environmental stresses such as hydrogen peroxide, acetic acid, and amphotericin B. Apoptosis is regulated by the calcineurin-caspase pathway in C. albicans, and calcineurin is under the control of Hsp90 in echinocandin resistance. However, the role of Hsp90 in apoptosis of C. albicans remains unclear. In this study, we investigated the role of Hsp90 in apoptosis of C. albicans by using an Hsp90-compromised strain tetO-HSP90/hsp90 and found that upon apoptotic stimuli, including hydrogen peroxide, acetic acid or amphotericin B treatment, less apoptosis occurred, less ROS was produced, and more cells survived in the Hsp90-compromised strain compared with the Hsp90/Hsp90 wild-type strain. In addition, Hsp90-compromised cells were defective in up-regulating caspase-encoding gene CaMCA1 expression and activating caspase activity upon the apoptotic stimuli. Investigations on the relationship between Hsp90 and calcineurin revealed that activation of calcineurin could up-regulate apoptosis but could not further down-regulate apoptosis in Hsp90-compromised cells, indicating that calcineurin was downstream of Hsp90. Hsp90 inhibitor geldanamycin (GdA) could further decrease the apoptosis in calcineurin-pathway-defect strains, indicating that compromising Hsp90 function had a stronger effect than compromising calcineurin function on apoptosis. Collectively, this study demonstrated that compromised Hsp90 reduced apoptosis in C. albicans, partially through downregulating the calcineurin-caspase pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / pharmacology
  • Amphotericin B / pharmacology
  • Antifungal Agents / pharmacology
  • Apoptosis* / drug effects
  • Benzoquinones / pharmacology
  • Calcineurin / metabolism*
  • Candida albicans / cytology*
  • Candida albicans / drug effects
  • Candida albicans / enzymology
  • Candida albicans / metabolism*
  • Caspases / metabolism*
  • Doxycycline / pharmacology
  • Enzyme Activation / drug effects
  • Fungal Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Lactams, Macrocyclic / pharmacology
  • Microscopy, Confocal
  • Signal Transduction* / drug effects


  • Antifungal Agents
  • Benzoquinones
  • Fungal Proteins
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Amphotericin B
  • Hydrogen Peroxide
  • Calcineurin
  • Caspases
  • Doxycycline
  • Acetic Acid
  • geldanamycin

Grant support

This work was supported by the National Natural Science Foundation of China (81072678, 30825041 and 90913008) and Postdoctoral Science Foundation of China (20110491851). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.