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

Increased intestinal colonization with Candida albicans is believed to be a major predisposing factor to systemic candidiasis. Previous evidence has i mplicated the C. albicans INT1 gene in hyphal development, epithelial adher ence, and mouse virulence. The effect of INT1 on mouse cecal colonization w as measured using a parent strain (CAF2, INT1/INT1), an int1 deletion homoz ygote (CAG3, int1/int1), and a heterozygous reintegrant (CAG5, int1/int1 INT1). Forty-eight hours after oral inoculation of 10(7) C. albicans into n ormal mice, only low numbers of each strain were recovered from the cecal f lora. In mice pretreated with oral bacitracin/streptomycin, cecal colonizat ion 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 homoz ygous mutants not different from each other. In mice pretreated with parent eral lipopolysaccharide (LPS), in addition to oral antibiotics, numbers of cecal CAF2, CAG5, and CAG3 were increased (P < 0.01) compared to the corres ponding 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 add itive effect on C. albicans cecal colonization in antibiotic-treated mice, and the presence of two functional copies of the INT1 gene appeared to faci litate colonization in both antibiotic-treated mice and in mice treated wit h antibiotics plus parenteral endotoxin.