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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
08:48

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis

Published on: March 19, 2019

The cellular target of histatin 5 on Candida albicans is the energized mitochondrion

E J Helmerhorst1, P Breeuwer, W van't Hof

  • 1Academic Centre for Dentistry, Department of Oral Biochemistry, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands. EJ.Helmerhorst.obc.acta@med.vu.nl

The Journal of Biological Chemistry
|March 6, 1999
PubMed

Insights

Histatin 5, a salivary peptide, kills Candida albicans by entering cells and targeting mitochondria. Its fungicidal action depends on cell metabolism and is inhibited by high salt.

Area of Science:

  • Biochemistry
  • Microbiology
  • Cell Biology

Background:

  • Histatin 5 is a human salivary peptide with known fungicidal properties against Candida albicans in vitro.
  • The precise mechanism of action for histatin 5's fungicidal activity remains incompletely understood.

Purpose of the Study:

  • To investigate the mechanism of action of histatin 5 on Candida albicans viability.
  • To determine the relationship between histatin 5's fungicidal and membrane-perturbing activities.
  • To elucidate the cellular localization and target of histatin 5 within Candida albicans.

Main Methods:

  • Studied the effect of histatin 5 on Candida albicans viability and membrane integrity using propidium iodide influx.
  • Assessed mitochondrial transmembrane potential using rhodamine 123.
  • Utilized labeled histatin 5 (TRITC or FITC) for intracellular localization studies, co-localizing with mitochondria-specific probes (Mitotracker Orange).
  • Investigated the influence of high salt conditions and metabolic inhibitors (sodium azide) on histatin 5 activity and uptake.

Main Results:

  • Histatin 5's fungicidal and membrane-perturbing activities were inhibited by high salt concentrations and metabolic inhibitors.
  • Exposure to histatin 5 led to a loss of mitochondrial transmembrane potential in Candida albicans cells.
  • Labeled histatin 5 showed granular intracellular distribution, co-localizing with mitochondria.
  • Uptake of labeled histatin 5 was also inhibited by mitochondrial inhibitors and high salt conditions.

Conclusions:

  • Histatin 5 is internalized by Candida albicans cells.
  • The energized mitochondrion is a primary target for histatin 5.
  • The fungicidal mechanism of histatin 5 involves mitochondrial disruption, dependent on cellular metabolic activity and salt concentration.

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