Corneal virulence of Candida albicans strains deficient in Tup1-regulated genes.
OBJECTIVE
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 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.


RESULTS
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.


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.
Jackson
Beth E
BE
Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
Mitchell
Bradley M
BM
Wilhelmus
Kirk R
KR
D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology* / Q000473:pathology; D015169:Colony Count, Microbial; D003315:Cornea / Q000382:microbiology*; D003320:Corneal Ulcer / Q000382:microbiology* / Q000473:pathology; D015821:Eye Infections, Fungal / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D020868:Gene Silencing; D051379:Mice; D008807:Mice, Inbred BALB C; D012097:Repressor Proteins / Q000235:genetics*; D014774:Virulence
D005656:Fungal Proteins; D012097:Repressor Proteins