Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To evaluate how the ten secreted aspartyl proteinases of Candida albicans affect experimental fungal keratitis.
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.
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.
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.
This PDF is available to Subscribers Only