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Updated: Jul 17, 2026

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
Published on: July 1, 2020
Candida albicans strain-dependent virulence and Rim13p-mediated filamentation in experimental keratomycosis
Bradley M Mitchell1, Tzu G Wu, Beth E Jackson
1Sid W. Richardson Ocular Microbiology Laboratory, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin, Houston, TX 77030, USA.
Purpose:
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.
Insights
Wild-type Candida albicans strains vary in virulence, with filamentation being key to corneal infection. A specific gene mutation (rim13) fully blocked virulence, highlighting its role in fungal eye infections.
Area of Science:
- Ophthalmology
- Mycology
- Infectious Diseases
Background:
- Candida albicans is a common cause of fungal keratitis.
- Fungal filamentation is a proposed virulence factor in C. albicans infections.
Purpose of the Study:
- Compare virulence of wild-type C. albicans strains in a murine corneal infection model.
- Investigate the role of fungal filamentation in disease progression.
Main Methods:
- BALB/c mice (immunocompetent and immunosuppressed) were inoculated with C. albicans strains or mutants.
- Corneal disease was assessed daily; fungal load and histopathology were analyzed.
Main Results:
- Significant differences in corneal disease severity were observed among wild-type strains.
- A rim13 mutant was fully attenuated, while a control mutant was virulent.
- Cyclophosphamide treatment increased susceptibility and partially rescued the rim13 mutant phenotype.
Conclusions:
- Ocular pathogenicity of C. albicans strains correlates with pseudohyphae/hyphae production and corneal invasion.
- The rim13 gene is a specific virulence factor for C. albicans in corneal infections, demonstrated by the mutant's attenuation.
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