Effect of INT1 gene on Candida albicans murine intestinal colonization

Background. Increased intestinal colonization with Candida albicans is beli eved to be a major factor predisposing immunocompromised and postsurgical p atients to systemic candidiasis, although the mechanisms facilitating C, al bicans colonization remain unclear. Because previous studies have linked th e C. albicans INT1 gene to filament formation, epithelial adherence, and mo use virulence, experiments were designed to evaluate the effect of INT1 on intestinal colonization. Materials and Methods, Mice were orally inoculated with either the parent s train (CAF2, INT/INT1), an int1 heterozygote (CAG1, INT1/int1), an int1 hom ozygote (CAG3, int1/int1), or a reintegrant (CAG5, int1/int1 + INT1), and s acrificed 3 and 7 days later for quantitative analysis of cecal C. albicans , Results. Following oral inoculation with 10(3) C. albicans, only small numb ers of each strain were recovered from the cecal flora of normal mice. Howe ver, in mice pretreated with oral antibiotics, cecal colonization of each s train 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 occ asional yeast forms appeared adherent to the intestinal epithelium. Conclusions, C. albicans readily colonized and replicated in the ceca of an tibiotic-treated mice. The presence of two functional copies of INT1 appear ed 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 intest inal colonization. (C) 1999 Academic Press.