Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

Abstract

In an effort to bring novel diagnostic and prognostic biomarkers or even potential targets for vaccine design for systemic candidiasis (SC) into the open, a systematic proteomic approach coupled with bioinformatic analysis was used to decode the serological response to Candida wall immunome in SC patients. Serum levels of IgG antibodies against Candida wall-associated proteins (proteins secreted from protoplasts in active wall regeneration, separated by two-dimensional gel electrophoresis, and identified by mass spectrometry) were measured in 45 SC patients, 57 non-SC patients, and 61 healthy subjects by Western blotting. Two-way hierarchical clustering and principal component analysis of their serum anti-Candida wall antibody expression patterns discriminated SC patients from controls and highlighted the heterogeneity of their expression profiles. Multivariate logistic regression models demonstrated that high levels of antibodies against glucan 1,3-␤-glucosidase (Bgl2p) and the antiwall phosphoglycerate kinase antibody seropositivity were the only independent predictors of SC. Receiver operating characteristic curve analysis revealed no difference between their combined evaluation and measurement of anti-Bgl2p antibodies alone. In a logistic regression model adjusted for known prognostic factors for mortality, SC patients with high anti-Bgl2p antibody levels or a positive anti-wall enolase antibody status, which correlated with each other, had a reduced 2-month risk of death. After controlling for each other, only the seropositivity for anti-wall enolase antibodies was an independent predictor of a lower risk of fatality, supporting that these mediated the protective effect. No association between serum anti-cytoplasmic enolase antibody levels and outcomes was established, suggesting a specific mechanism of enolase processing during wall biogenesis. We conclude that serum anti-Bgl2p antibodies are a novel accurate diagnostic biomarker for SC and that, at high levels,

Amyloid-like properties ofSaccharomyces cerevisiaecell wall glucantransferase Bgl2p

“…In pathogenic yeasts it participates in virulence 10 and a high Bgl2p antibody titre is a marker of systemic candidiasis. 11 Here we demonstrated that Bgl2p possess amyloidogenic features. Firstly-low solubility in SDS and resistance to protease digestion are considered to be www.landesbioscience.com Prion 93…”

Candida albicansCell Wall Proteins

“…Several studies have investigated the subproteome of the cell surface (73,87,301,303,380,391; M. Martínez-Gomariz, P. Perumal, S. Mekala, C. Nombela, C. Gil, and W. L. Chaffin, unpublished data). Fractionation of this subproteome employed various extraction procedures from either intact organisms or isolated cell walls.…”

CotH3 mediates fungal invasion of host cells during mucormycosis

“…Protoplasts were collected by centrifugation for 5 minutes at 200 g at 4°C, washed twice with 0.5 M sorbitol, and resuspended in the same buffer. Incubating protoplasts in the presence of the osmotic stabilizer sorbitol enables regeneration of the cell wall, and during regeneration, cell wall constituents are released into the supernatant (41,42). After a 2-hour incubation period (43), protoplasts were pelleted, and the supernatant was sterilized by filtration (0.22-μm filters) in the presence of protease inhibitors (Pierce).…”