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B.E. Jackson, K.R. Wilhelmus, B.M. Mitchell; Ocular Virulence of Candida albicans Strains . Invest. Ophthalmol. Vis. Sci. 2006;47(13):297.
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To evaluate virulence of Candida albicans homozygous mutants in a murine keratitis model.
Corneas of 3–5 immunocompetent adult female BALB/c mice were topically inoculated with a wild–type strain of C. albicans, a transposon–induced homozygous mutant (rbt1–/–), its parental control (DAY286), knockout homozygous mutants BCa7–4 (rbt1–/–) and BCa11–3 (rbt4–/–), or its parental control (CAF2–1). The fungal load inoculated onto the cornea was at concentrations of 105 or 106 colony–forming units (cfu) following corneal scarification. Mock–inoculated, scarified eyes served as controls. Eyes were scored daily for 8 days post infection (PI) using a 12–point scale to categorize corneal disease.
At 106 cfu, wild–type C. albicans human isolate (SC5314) had a high degree of virulence in the murine cornea, and the fungal strains used to generate the mutants (DAY286 and CAF2–1) had similar corneal pathogenicity (P > 0.43 and > 0.11, respectively). Likewise, the rbt1–/– mutant had no significant differences in keratitis score when compared to SC5314 (P > 0.13). There was no significant difference with BCa7–4 when compared to SC5314 (P > 0.169), until 5 days PI (P < 0.024). BCa11–3 partially attenuated virulence in the mouse cornea and had a significant difference in disease severity when compared to SC5314 at every time point (P < 0.037).
While BCa7–4 and BCa11–3 had fully attenuated fungal virulence in a mouse systemic infection model, only BCa11–3 showed partially attenuated virulence in murine fungal keratitis; rbt1–/– had no variation when compared to wild–type strains. The genetic control of ocular virulence by C. albicans differs, in part, from virulence of systemic candidiasis.
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