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B.M. Mitchell, T.G. Wu, K.R. Wilhelmus; Strain-Dependent Virulence Differences of Candida albicans in Experimental Keratomycosis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1411.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To compare the virulence of different strains of Candida albicans in a murine model and to develop a marker rescue system to identify virulence factors for fungal keratitis. Methods: The in vitro growth kinetics of three different wild-type strains of C. albicans (SC5314, B311, VE175) isolated from human infections were compared by spectrophotometric analysis of cultures in Sabouraud dextrose broth. Ocular virulence for the three strains was determined using a mouse model for experimental keratomycosis. Adult BALB/c mice were unilaterally inoculated with 1 x 106 colony-forming units of C. albicans following corneal scarification. Mock-infected eyes inoculated with sterile culture media served as controls. Corneal inflammation was categorized daily for 8 days. Eyes were enucleated for quantitative fungal cultures at 0.25, 1, 4, and 8 days post inoculation and histologically evaluated at 1 and 4 days. Results: All three strains of C. albicans exhibited similar growth kinetics in vitro. Based upon quantitative microbial culturing, all three strains were cleared from the ocular tissues with similar kinetics; however, there was a gradation in the severity of keratomycosis. SC5314 was the most virulent strain, VE175 the least virulent, and B311 intermediate in virulence. The severity of corneal disease among the strains was significantly different (P<0.003). Histopathological analysis was consistent with disease scores. SC5314 was the most invasive strain with organisms found in the deeper layers of corneal stroma and extension into of the anterior chamber. Inflammatory cells and stromal necrosis were also more prominent in corneas infected with SC5314 compared to B311 or VE175. VE175 was the least invasive and typically had minimal inflammation or stromal involvement. Conclusions: Different strains of C. albicans demonstrated significantly different levels of virulence in a mouse model for keratomycosis. No measurable growth differences or apparent differences in corneal adherence during early time-points of infection were observed. These results suggest that genetic determinants for virulence and ocular pathogenesis differ among strains of C. albicans, which might explain in part the variable degree of clinical disease seen in humans. Recombinant yeast generated between the high virulent SC5314 and low virulent VE175 strains should prove to be invaluable in marker rescue studies to identify specific genetic elements that contribute to fungal virulence during ocular infection.
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