Effect of oral tetracycline, the microbial flora, and the athymic state on gastrointestinal colonization and infection of BALB/c mice with Candida albicans

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Abstract
Scanning electron microscopy, light microscopy, and quantitative culture of microorganisms in intestinal contents were used to determine the effects of oral tetracycline, the bacterial flora of conventionally reared animals (conventional), and thymus-dependent immune competency on the capacity of Candida albicans to colonize and infect the gastrointestinal tract of four groups of mice: thymus-intact conventional mice, conventional athymic mice, flora-defined athymic mice, and thymus-intact bacteria-free mice. Thymus-intact conventional mice without antibiotic treatment began to shed C. albicans less than 48 h after oral yeast challenge and were devoid of detectable yeast by day 16. Tetracycline altered the bacterial flora qualitatively and quantitatively, allowing C. albicans to colonize in less than 48 h and to persist in the gut tract for 32 days. Only 2 of 72 of these conventional mice developed candidiasis (hyphal infection). Although tetracycline altered the bacterial flora of conventional athymic (nude) mice, it was not required to allow C. albicans to colonize their gut tract to levels significantly higher than those in thymus-intact conventional mice. All conventional nude mice were consistently colonized and 14 of 24 animals showed an increased yeast colonization of the keratinized stomach, but only 3 of 24 developed gastric candidiasis. Flora-defined athymic (nude) mice had significantly lower aerobic bacterial levels and significantly higher C. albicans levels in the gut contents than conventional athymic mice. The flora-defined nude mice, however, developed gastric candidiasis by day 5. Thymus-intact bacteria-free mice were uniformly colonized and infected with C. albicans less than 48 h after oral challenge regardless of tetracycline treatment. Populations of C. albicans in the gut of bacteria-free mice were significantly higher than in the gut tract of the thymus-intact conventional or athymic mice. Gastric mycelial infection was detected in 8 of 10 bacteria-free animals 2 days after oral challenge. By 32 days, 45 of 50 mice of both tetracycline-treated and control bacteria-free groups were infected with C. albicans. These data indicate that a competive bacteria flora is more effective than an intact immune system in preventing gastric candidiasis and that an immune deficiency may allow increased yeast colonization of the keratinized and glandular stomach epithelium. Tetracycline did not appear to enhance the invasiveness or pathogenicity of C. albicans in mice even though it facilitates yeast-phase gut colonization in conventionally reared mice.