Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and

Angela A Sanchez1, Douglas A Johnston, Carter Myers

  • 1St. Johns Cardiovascular Research Center, Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 90502, USA.

Infection and Immunity
|December 23, 2003
PubMed

Insights

Candida albicans uses endothelial cell damage to cause invasive infections. An in vitro assay screening for this damage effectively identified key virulence factors for disseminated candidiasis.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pathogenesis

Background:

  • Candida albicans is a fungal pathogen that can cause life-threatening disseminated infections.
  • Vascular invasion by C. albicans requires penetration of the endothelial cell lining.
  • Understanding the mechanisms of endothelial cell damage is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of endothelial cell damage in C. albicans pathogenesis.
  • To evaluate an in vitro endothelial cell damage assay as a screening tool for identifying C. albicans virulence factors.

Main Methods:

  • A library of 27 C. albicans mutants was generated and compared to the wild-type parent strain.
  • Endothelial cell damage was assessed in vitro using the mutant library.
  • The virulence of selected mutants was evaluated in a murine model of hematogenously disseminated candidiasis following tail vein inoculation.

Main Results:

  • Ten C. albicans mutants exhibited significantly impaired endothelial cell damage in vitro.
  • All ten mutants with reduced endothelial cell damage showed attenuated virulence in the murine infection model.
  • A strong correlation was observed between the capacity to damage endothelial cells and the ability to cause lethal infection.

Conclusions:

  • Endothelial cell damage is a critical factor in the pathogenesis of hematogenously disseminated candidiasis.
  • The in vitro endothelial cell damage assay serves as a reliable screening method for identifying C. albicans virulence factors.
  • This assay can aid in the discovery of novel therapeutic targets for invasive candidiasis.