Corneal Virulence of Candida albicans Strains Deficient in Tup1-Regulated Genes

• Published in: Investigative ophthalmology & visual science Vol. 48; no. 6; pp. 2535 - 2539
• Main Authors: Jackson, Beth E, Mitchell, Bradley M, Wilhelmus, Kirk R
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.06.2007; Association for Research in Vision and Ophtalmology
• Subjects: Animals; Biological and medical sciences; Candida albicans - genetics; Candida albicans - pathogenicity; Candidiasis - microbiology; Candidiasis - pathology; Colony Count, Microbial; Cornea - microbiology; Corneal Ulcer - microbiology; Corneal Ulcer - pathology; Eye and associated structures. Visual pathways and centers. Vision; Eye Infections, Fungal - microbiology; Eye Infections, Fungal - pathology; Female; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Gene Expression Regulation, Fungal - physiology; Gene Silencing; Mice; Mice, Inbred BALB C; Repressor Proteins - genetics; Vertebrates: nervous system and sense organs; Virulence; Fungi; Candida albicans; Cornea; Regulation(control); Gene; Deficiency; Virulence; Fungi Imperfecti; Ophthalmology; Thallophyta; Strain
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.06-0909

To evaluate the role of rbt genes downstream of Tup1p, a transcription factor regulating fungal filamentation, in experimental Candida albicans keratitis. Corneas of BALB/c mice were scarified and topically inoculated with 10(5) or 10(6) 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. With a 10(5) 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 10(6) 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. 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.