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

Beth E Jackson1, Bradley M Mitchell, Kirk R Wilhelmus

  • 1Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.

Investigative Ophthalmology & Visual Science
|May 26, 2007
PubMed
Abstract

Insights

The Candida albicans rbt4 gene is a virulence factor in experimental fungal keratitis. Hyphal morphogenesis is crucial for the initial stages of this posttraumatic corneal infection.

Area of Science:

  • Microbiology
  • Ophthalmology
  • Genetics

Background:

  • Candida albicans is a common cause of fungal keratitis, a serious posttraumatic corneal infection.
  • Tup1p is a transcription factor that regulates fungal filamentation, a key process in C. albicans pathogenesis.
  • The role of genes downstream of Tup1p, specifically rbt genes, in C. albicans keratitis is not well understood.

Purpose of the Study:

  • To investigate the role of rbt genes, regulated by Tup1p, in experimental Candida albicans keratitis.
  • To determine if rbt gene mutations affect the severity and progression of fungal keratitis in a mouse model.

Main Methods:

  • Experimental keratitis was induced in BALB/c mice by topical inoculation with wild-type C. albicans or various rbt gene mutant strains.
  • Mice corneas were inoculated with different colony-forming units (CFU) of C. albicans strains.
  • Clinical severity of keratitis was scored daily, and eyes were examined histopathologically.

Main Results:

  • At a lower inoculum (10^5 CFU), rbt1 and rbt4 mutants showed significantly lower keratitis scores compared to wild-type strains.
  • At a higher inoculum (10^6 CFU), all strains induced severe disease except for the rbt4-deficient mutant (BCa11-3), which caused moderate, resolving disease.
  • The rbt1 mutant (Tn7-rbt1) induced keratitis severity comparable to wild-type strains, while another rbt1 mutant (BCa7-4) initially caused severe disease that waned.

Conclusions:

  • The rbt4 gene is identified as a potential virulence factor in posttraumatic Candida albicans keratitis.
  • Genetically regulated hyphal morphogenesis plays a role in the initial pathogenesis of experimental fungal keratomycosis.

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