Effect of INT1 gene on Candida albicans murine intestinal colonization.
BACKGROUND
Increased intestinal colonization with Candida albicans is believed to be a major factor predisposing immunocompromised and postsurgical patients to systemic candidiasis, although the mechanisms facilitating C. albicans colonization remain unclear. Because previous studies have linked the C. albicans INT1 gene to filament formation, epithelial adherence, and mouse virulence, experiments were designed to evaluate the effect of INT1 on intestinal colonization.


METHODS
Mice were orally inoculated with either the parent strain (CAF2, INT/INT1), an int1 heterozygote (CAG1, INT1/int1), an int1 homozygote (CAG3, int1/int1), or a reintegrant (CAG5, int1/int1 + INT1), and sacrificed 3 and 7 days later for quantitative analysis of cecal C. albicans.


RESULTS
Following oral inoculation with 10(3) C. albicans, only small numbers of each strain were recovered from the cecal flora of normal mice. However, in mice pretreated with oral antibiotics, cecal colonization of each strain was increased (P < 0.01). In addition, cecal colonization was reduced for all int1 mutant strains compared with the parent strain (P < 0.05). By light microscopy, all four C. albicans strains were easily observed in the ileal lumen as both budding yeast and filamentous forms, although only occasional yeast forms appeared adherent to the intestinal epithelium.


CONCLUSIONS
C. albicans readily colonized and replicated in the ceca of antibiotic-treated mice. The presence of two functional copies of INT1 appeared to facilitate C. albicans cecal colonization, suggesting that intestinal colonization may be another virulence factor associated with INT1 and that the gene product may be an attractive target to control C. albicans intestinal colonization.
Kinneberg
K M
KM
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
Bendel
C M
CM
Jechorek
R P
RP
Cebelinski
E A
EA
Gale
C A
CA
Berman
J G
JG
Erlandsen
S L
SL
Hostetter
M K
MK
Wells
C L
CL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002176:Candida albicans / Q000235:genetics / Q000502:physiology*; D002432:Cecum / Q000382:microbiology; D005260:Female; D005800:Genes, Fungal / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007082:Ileum / Q000473:pathology; D007422:Intestines / Q000382:microbiology*; D051379:Mice
D000900:Anti-Bacterial Agents