Ecm7, a regulator of HACS, functions in calcium homeostasis maintenance, oxidative stress response and hyphal development in Candida albicans

Fungal Genet Biol. 2013 Aug:57:23-32. doi: 10.1016/j.fgb.2013.05.010. Epub 2013 Jun 13.

Abstract

Calcium is a universal messenger that translates diverse environmental stresses and developmental cues into specific cellular and developmental responses. In yeast, Cch1 and Mid1 function as part of a high affinity Ca²⁺ influx system (HACS) that becomes activated rapidly in response to sudden stimuli. Here, we report that Ecm7, a regulator of HACS, plays important roles in calcium homeostasis maintenance, oxidative stress response and hyphal development in Candida albicans. Disruption of ECM7 led to increased sensitivity to calcium-depleted conditions. Flow cytometry analysis revealed that Ecm7 mediated Ca²⁺ influx under high pH shock. Cycloheximide chase experiments further showed that MID1 deletion significantly decreased the stability of Ecm7. We also provided evidences that ecm7Δ/Δ cells were hypersensitive to oxidative stress. ECM7 deletion induced the degradation of Cap1 when exposed to H₂O₂ treatment. Besides, the ecm7Δ/Δ mutant showed a defect in hyphal development, which was accompanied with the decreased expression of hyphal related gene HWP1. Though subsequent experiments revealed that the ecm7Δ/Δ mutant showed similar virulence to the wild-type strain, the ability of invasion and diffusion of the mutant in mouse kidneys decreased. Taken together, Ecm7 plays important roles in the adaptation and pathogenicity of C. albicans.

Keywords: 2′,7′-dichlorodihydrofluorescein diacetate; 5-FOA; 5-fluoroorotic acid; CHX; Calcium homeostasis; Candida albicans; DCFH-DA; EGTA; Ecm7; FBS; HACS; HBSS; Hank’s balanced salt solution; Hyphal development; Oxidative stress; SC; SD; VGCC; Virulence; cycloheximide; ethylene glycol bis(2-aminoethyl) tetraacetic acid; fetal bovine serum; high affinity Ca(2+) influx system; synthetic complete; synthetic drop-out; voltage-gated calcium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / genetics*
  • Candida albicans / genetics*
  • Candida albicans / growth & development
  • Candida albicans / pathogenicity
  • Candidiasis
  • Fungal Proteins / genetics*
  • Gene Expression Regulation, Fungal
  • Hydrogen Peroxide
  • Hydrogen-Ion Concentration
  • Hyphae / genetics
  • Hyphae / growth & development
  • Hyphae / pathogenicity
  • Membrane Proteins / genetics*
  • Mice
  • Oxidative Stress*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development

Substances

  • Fungal Proteins
  • Membrane Proteins
  • Hydrogen Peroxide
  • Calcium