Candida albicans strain-dependent virulence and Rim13p-mediated filamentation in experimental keratomycosis.
OBJECTIVE
To compare the virulence of wild-type Candida albicans strains in a murine model of corneal candidiasis and to investigate the role of fungal filamentation in disease progression.


METHODS
Scarified corneas of immunocompetent or cyclophosphamide-treated BALB/c mice were topically inoculated with one of three human isolates of C. albicans, a homozygous mutant of the pH-dependent filamentation gene rim13 or a mutant reference strain control. Mock-inoculated eyes served as negative controls. Corneal disease was categorized daily for 8 days with quantitative fungal culturing of eyes at 6 hours, 1 day, 4 days, and 8 days after infection and histopathologic examination at 1 day and 4 days after infection.


RESULTS
Corneal disease severity differed significantly among wild-type strains (P < or = 0.02). The rim13(-/-) mutant Tn7-rim13 was fully attenuated, whereas the mutant control DAY286 was fully virulent. Pretreatment of mice with cyclophosphamide increased susceptibility to wild-type C. albicans and partially rescued the attenuated phenotype of the genetically deficient rim13(-/-) fungal mutant. All strains replicated with similar kinetics in vitro, and wild-type strains had similar clearance from infected eyes. Histopathologic findings correlated with disease severity.


CONCLUSIONS
Wild-type strains of C. albicans that differ significantly in ocular pathogenicity correlate with the ability of yeast to produce pseudohyphae and hyphae and to invade corneal tissue. Full attenuation of the fungal rim13(-/-) mutant is the first direct demonstration of a hyphal morphogenesis-related gene as a specific virulence factor for C. albicans during corneal infection.
Mitchell
Bradley M
BM
Sid W. Richardson Ocular Microbiology Laboratory, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin, Houston, TX 77030, USA.
Wu
Tzu G
TG
Jackson
Beth E
BE
Wilhelmus
Kirk R
KR
D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology* / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D015821:Eye Infections, Fungal / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005656:Fungal Proteins / Q000502:physiology*; D005800:Genes, Fungal / Q000502:physiology; D025301:Hyphae / Q000472:pathogenicity*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007634:Keratitis / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014774:Virulence
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D007166:Immunosuppressive Agents; C489602:RIM101 protein, Candida albicans; D003520:Cyclophosphamide