The Candida albicans INT1 gene facilitates cecal colonization in endotoxin-treated mice

Shock. 2000 Jun;13(6):453-8. doi: 10.1097/00024382-200006000-00006.

Abstract

Increased intestinal colonization with Candida albicans is believed to be a major predisposing factor to systemic candidiasis. Previous evidence has implicated the C. albicans INT1 gene in hyphal development, epithelial adherence, and mouse virulence. The effect of INT1 on mouse cecal colonization was measured using a parent strain (CAF2, INT1/INT1), an int1 deletion homozygote (CAG3, int1/int1), and a heterozygous reintegrant (CAG5, int1/int1 + INT1). Forty-eight hours after oral inoculation of 10(7) C. albicans into normal mice, only low numbers of each strain were recovered from the cecal flora. In mice pretreated with oral bacitracin/streptomycin, cecal colonization of each C. albicans strain was increased compared to the corresponding strain inoculated into untreated mice, with the CAF2 parent strain greater (P < 0.01) than the two mutant strains, and with the heterozygous and homozygous mutants not different from each other. In mice pretreated with parenteral lipopolysaccharide (LPS), in addition to oral antibiotics, numbers of cecal CAF2, CAG5, and CAG3 were increased (P < 0.01) compared to the corresponding strain inoculated into mice treated with antibiotics alone. In LPS-treated mice, numbers of cecal C. albicans CAF2 (INT1/INT1) were greater (P < 0.05) than C. albicans CAG3 (int1/int1). Thus, parenteral LPS had an additive effect on C. albicans cecal colonization in antibiotic-treated mice, and the presence of two functional copies of the INT1 gene appeared to facilitate colonization in both antibiotic-treated mice and in mice treated with antibiotics plus parenteral endotoxin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacitracin / toxicity
  • Candida albicans / genetics*
  • Candida albicans / pathogenicity
  • Candida albicans / physiology
  • Candidiasis / etiology*
  • Cecum / microbiology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Drug Therapy, Combination / toxicity
  • Fungal Proteins*
  • Gene Deletion
  • Genotype
  • Lipopolysaccharides / toxicity*
  • Lymph Nodes / microbiology
  • Mice
  • Streptomycin / toxicity
  • Superinfection
  • Virulence / genetics

Substances

  • Cell Adhesion Molecules
  • Fungal Proteins
  • Lipopolysaccharides
  • alphaINT1 protein, Candida albicans
  • Bacitracin
  • Streptomycin