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Beth E. Jackson, Bradley M. Mitchell, Kirk R. Wilhelmus; Corneal Virulence of Candida albicans Strains Deficient in Tup1-Regulated Genes. Invest. Ophthalmol. Vis. Sci. 2007;48(6):2535-2539. doi: 10.1167/iovs.06-0909.
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purpose. To evaluate the role of rbt genes downstream of Tup1p, a transcription factor regulating fungal filamentation, in experimental Candida albicans keratitis.
methods. Corneas of BALB/c mice were scarified and topically inoculated with 105 or 106 colony-forming units (CFU) of a wild-type human isolate of C. albicans (SC5314), a mutant strain with a transposon-induced homozygous disruption of the rbt1 gene (Tn7-rbt1), its control (DAY286), homozygous rbt knockout mutants deficient in rbt1 (BCa7-4) or rbt4 (BCa11-3), or their parental control (CAF2-1). Eyes were scored daily for clinical severity of fungal keratitis and were examined histopathologically.
results. With a 105 CFU inoculum, the CAF2-1 control and its mutant derivatives (BCa7-4 and BCa11-3) produced significantly lower keratitis scores than did the moderately severe keratitis induced by control strains SC5314 and DAY286 and the Tn7-rbt1 mutant (P < 0.05). At a 106 CFU inoculum, all strains induced severe disease except for the rbt4-deficient mutant. Fungal keratitis caused by Tn7-rbt1 was as severe as that of control strains (P > 0.2), and the BCa7-4 mutant initially caused severe disease that gradually waned (P < 0.02). However, the BCa11-3 mutant produced moderate disease that was significantly less severe than that induced by control strains (P < 0.04) and resolved within 1 week.
conclusions. The rbt4 gene of C. albicans is a potential virulence factor in posttraumatic corneal infection. Genetically regulated hyphal morphogenesis appears to be involved in the initial pathogenesis of experimental keratomycosis.
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