May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
EFG1-Regulated SAP6 Proteinase is Required for Progressive Infection of Posttraumatic Candida albicans Keratitis
Author Affiliations & Notes
  • B. E. Jackson
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • K. R. Wilhelmus
    Ophthalmology, Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships B.E. Jackson, None; K.R. Wilhelmus, None.
  • Footnotes
    Support Institutional research training grant (EY07001) and core grant (EY02520) from the NEI, the Research to Prevent Blindness, Inc., the Lions Eye Bank Foundation, and the Sid W. Richardson Foundation
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 721. doi:
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      B. E. Jackson, K. R. Wilhelmus; EFG1-Regulated SAP6 Proteinase is Required for Progressive Infection of Posttraumatic Candida albicans Keratitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):721.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: To evaluate how the ten secreted aspartyl proteinases of Candida albicans affect experimental fungal keratitis.

Methods:: For each yeast strain, corneas of 3-5 immunocompetent adult female BALB/c mice were superficially scarified then topically inoculated with 106 colony-forming units (cfu) of a wild-type strain of C. albicans, a parental control strain, or a secreted aspartyl proteinase (sap) homozygous mutant, including 2 triple mutants (sap1-3-/- and sap4-6-/-), 4 double mutants (sap9/10-/-, sap4/5-/-, sap4/6-/-, sap5/6-/-), 3 single mutants (sap4-/-, sap5-/-, sap6-/-), and a sap6 rescuant. Mock-inoculated, scarified eyes served as controls. Eyes were scored daily for 8 days post-infection to categorize corneal disease. Growth kinetics on yeast-peptone dextrose and selective (SCD-Ura) media were also examined for each fungal strain.

Results:: Wild-type (SC5314) and parental (CAF-2) C. albicans strains produced a high degree of virulence in the murine cornea. Similarly, sap1-3-/- and sap9/10-/- mutants had severe keratitis scores when compared to SC5314 (P > 0.25 and > 0.28, respectively). However, fungi lacking sap4-6 produced a moderate infection that cleared completely (P < 0.001). Two double mutants (sap4/6-/- and sap5/6-/-) had partial attenuation, while sap4/5-/- produced similar disease severity as wild-type fungi. Minimal disease occurred at 1 day for the sap6-deficient mutant and cleared rapidly, and the sap6 rescuant increased disease severity back toward wild-type virulence. No growth advantage or disadvantage was seen for any strain in vitro.

Conclusions:: The sap6 gene of C. albicans encodes a unique secreted aspartyl proteinase that affects corneal pathogenicity, apparently by co-regulating the morphogenic switch from yeasts to pseudohyphae and hyphae during tissue invasion. This pathway offers a new target for antimicrobial control of candidiasis of the eye.

Keywords: fungal disease • microbial pathogenesis: experimental studies • keratitis 

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