Influence of Glucose on Candida albicans and the Relevance of the Complement FH-Binding Molecule Hgt1 in a Murine Model of Candidiasis

Influence of Glucose on Candida albicans and the Relevance of the Complement FH-Binding Molecule Hgt1 in a Murine Model of Candidiasis

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Candidiasis is common BED in diabetic patients.Complement evasion is facilitated by binding complement factor H (FH).Since the expression of high-affinity glucose transporter 1 (Hgt1), a FH-binding molecule, is glucose-dependent, we aimed to study its relevance to the pathogenesis of Candida albicans.

Euglycemic and diabetic mice were intravenously challenged with either Candida albicans lacking Hgt1 (hgt1-/-) or its parental strain (SN152).Survival and clinical status were monitored over 14 days.In vitro, Candida albicans strains were grown at different glucose concentrations, opsonized with human serum, and checked for C3b/iC3b and FH deposition.

Phagocytosis was studied by fluorescein isothiocyanate-labeled opsonized yeast cells incubated with granulocytes.The murine model demonstrated a significantly higher virulence of SN152 in diabetic mice and an overall increased lethality of mice challenged with hgt1-/-.In vitro lower phagocytosis and C3b/iC3b deposition and higher FH deposition were demonstrated for SN152 incubated at higher Forearm Crutches glucose concentrations, while there was no difference on hgt1-/- at physiological glucose concentrations.

Despite C3b/iC3b and FH deposition being glucose-dependent, this effect has a minor influence on phagocytosis.The absence of Hgt1 is diminishing this dependency on complement deposition, but it cannot be attributed to being beneficial in a murine model.