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Updated: May 2, 2026
Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
Lectin-Fc(IgG) fusion proteins exhibit antifungal activity against the emerging multidrug-resistant pathogen Candida
Susana Ruiz Mendoza1,2, Leandro Honorato3, Deborah Santos Cintra1,4
1Laboratório de Bioquímica e Imunologia das Micoses, Departamento de Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Niterói, Brazil.
Abstract:
Candida auris is an emerging fungal pathogen recognized among the Centers for Disease Control and Prevention's urgent threats and designated a critical priority by the World Health Organization due to its global spread, high mortality rates, potential for pan-drug resistance, and its persistent transmission within healthcare settings. The clinical management of C. auris infections is further hindered by the lack of both rapid/specific diagnosis and effective antifungals. These challenges emphasize the urgent need for alternative therapeutic strategies. In this study, we investigated the antifungal, immunomodulatory, and protective effects of engineered Lectin-Fc(IgG) fusion proteins against a fluconazole-resistant C. auris strain. Specifically, Dectin-1-Fc(IgG2a), Dectin-1-Fc(IgG2b), and wheat germ agglutinin (WGA)-Fc(IgG2a) demonstrated dose-dependent binding to key fungal cell wall components, β-1,3-glucan and chitin, with Dectin-1-Fc(IgG2b) exhibiting the highest reactivity, followed by Dectin-1-Fc(IgG2a) and WGA-Fc(IgG2a). In vitro, all constructs exhibited fungistatic activity and reduced the biofilm biomass and metabolism, with the Dectin-1-Fc(IgG) variants displaying the most potent effects. As opsonins, Lectin-Fc(IgG)s significantly enhanced the macrophage-yeast association and macrophage-mediated killing of C. auris. In a systemic murine C. auris infection model, a single therapeutic administration of Dectin-1-Fc(IgG2b) or WGA-Fc(IgG2a) conferred 100% protection, while Dectin-1-Fc(IgG2a) achieved >80% protection, with all treated mice manifesting clinical improvement. Quantification of fungal burden at day 7 post-infection revealed at least a ~1 log reduction in colony-forming units in the spleen, kidney, and liver of Lectin-Fc(IgG)-treated animals. Cytokine profiling indicated a Th1-type-skewed immune response in Lectin-Fc(IgG)-treated mice. Collectively, these findings support the antifungal and immunotherapeutic potential of Lectin-Fc(IgG)s against C. auris, offering a novel broad-spectrum strategy to overcome current therapeutic limitations.
Insights
Engineered Lectin-Fc fusion proteins show promise against drug-resistant Candida auris. These proteins demonstrated antifungal activity, enhanced immune response, and provided significant protection in a mouse model, offering a novel therapeutic strategy.
Area of Science:
- Mycology
- Immunology
- Biotechnology
Background:
- Candida auris is a critical global health threat due to its resistance to antifungals and high mortality rates.
- Current treatment options for C. auris infections are limited by diagnostic challenges and antifungal resistance.
- There is an urgent need for novel therapeutic strategies to combat C. auris.
Purpose of the Study:
- To investigate the antifungal, immunomodulatory, and protective effects of engineered Lectin-Fc(IgG) fusion proteins against fluconazole-resistant Candida auris.
- To assess the binding affinity of Dectin-1-Fc(IgG) and WGA-Fc(IgG) constructs to fungal cell wall components.
- To evaluate the efficacy of Lectin-Fc(IgG)s in vitro and in a systemic murine infection model.
Main Methods:
- Engineered Dectin-1-Fc(IgG2a), Dectin-1-Fc(IgG2b), and WGA-Fc(IgG2a) fusion proteins were designed and synthesized.
- Binding affinity to beta-1,3-glucan and chitin was assessed.
- In vitro antifungal activity, biofilm inhibition, and macrophage-mediated killing were evaluated.
- A systemic murine model of C. auris infection was used to assess therapeutic protection and fungal burden reduction.
Main Results:
- Lectin-Fc(IgG) constructs showed dose-dependent binding to fungal cell wall components, with Dectin-1-Fc(IgG2b) exhibiting the highest reactivity.
- All constructs displayed fungistatic activity, reduced biofilm biomass and metabolism in vitro.
- Lectin-Fc(IgG)s enhanced macrophage association and killing of C. auris.
- Therapeutic administration of Dectin-1-Fc(IgG2b) or WGA-Fc(IgG2a) conferred 100% protection in mice, with significant reduction in fungal burden and improved clinical outcomes.
- A Th1-type immune response was observed in treated mice.
Conclusions:
- Engineered Lectin-Fc(IgG) fusion proteins possess significant antifungal and immunotherapeutic potential against Candida auris.
- These fusion proteins offer a novel, broad-spectrum strategy to overcome limitations of current antifungal therapies.
- Lectin-Fc(IgG)s represent a promising avenue for developing new treatments for challenging C. auris infections.
