A mouse model for Candida glabrata hematogenous disseminated infection starting from the gut: evaluation of strains with different adhesion properties

PLoS One. 2013 Jul 23;8(7):e69664. doi: 10.1371/journal.pone.0069664. Print 2013.

Abstract

Adhesion to digestive mucosa is considered a crucial first step in the pathogenicity of invasive Candida infections. Candida glabrata disseminated infections predominantly start from the gut. A mouse model of disseminated infection starting from the gut was set up. Hematogenous dissemination was obtained after a low-protein diet followed by a regimen of cyclophosphamide-methotrexate and an oral inoculation of the yeasts via the drinking water. The liver was the first organ infected (day 7 post-infection), and lethality was 100% at day 21 post-infection. This new mouse model was used to compare the mortality rate and fungal burden in deep organs induced by 5 strains exhibiting different levels of adhesion to enterocyte Caco-2 cells, as determined in a test on 36 C. glabrata strains. In this model, no statistical difference of lethality was demonstrated between the strains, and fungal burden varied in kidneys and lungs but without correlation with the level of adhesion to enterocytes. Further studies using the model developed here allow analysis of the crossing of the digestive mucosa by yeasts, and help relate this to yet-poorly understood adhesion phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caco-2 Cells
  • Candida glabrata / physiology*
  • Candidiasis / microbiology*
  • Candidiasis / pathology*
  • Cell Adhesion
  • Colony Count, Microbial
  • Disease Models, Animal
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / pathology*
  • Humans
  • Kinetics
  • Mice
  • Survival Analysis

Grants and funding

Ralitsa Atanasova was the recipient of a PhD grant from the DIM Maladies Infectieuses, Ile de France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.