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(Investigative Ophthalmology and Visual Science. 2007;48:2535-2539.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0909
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Corneal Virulence of Candida albicans Strains Deficient in Tup1-Regulated Genes

Beth E. Jackson, Bradley M. Mitchell, and Kirk R. Wilhelmus

From the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.

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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