Systemic infection following intravenous inoculation of mice with Candida albicans int1 mutant strains

The Candida albicans gene INT1 is associated with epithelial adhesion, hyph al formation, and virulence. C. albicans strains carrying two, one, or no f unctional INT1 alleles were used to assess the association between mortalit y and C. albicans persistence in the liver and kidney of intravenously inoc ulated mice. Mice were injected with 10(5) C. albicans CAF2 (parent strain, INT1/INT1), C. albicans CAG3 (homozygous disruptant, Int1/int1), or C. alb icans CAGE (heterozygous reintegrant, int1/int1 + INT1). Mortality was moni tored and mice were sacrificed on Days 1, 7, 14, and 21 for quantitative an alysis of kidney and liver microbes, with histologic analysis of these tiss ues as well. Mortality was highest for mice injected with the wild-type str ain CAF2 (INT1/INT1) and lowest for mice injected with the homozygous disru ptant CAG3 (int/int1). Yeast were readily cleared from the liver of all mic e injected with any of the three C. albicans strains. Although the mutant s trains CAG3 and CAGE are defective for hyphal formation in vitro, there was histological evidence of abundant hyphal formation in the renal pelvis of mice injected with these strains. Compared to the wild-type strain, mutant strains were associated with reduced mortality but increased C. albicans pe rsistence in the kidney. Thus, the absolute ability to form hyphae in the k idney did not appear to modulate either C. albicans-induced mortality or th e course of progressive infection in the kidney. In addition, reduced virul ence was paradoxically associated with increased, not decreased, persistenc e of C. albicans in the kidney. (C) 1999 Academic Press.