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Updated: Jul 29, 2025
CRISPR-mediated Genome Editing of the Human Fungal Pathogen Candida albicans
Published on: November 14, 2018
Sequence Variation of Candida albicans Sap2 Enhances Fungal Pathogenicity via Complement Evasion and Macrophage
Lan Lin1, Moran Wang2, Jingsi Zeng3
1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
Abstract:
Candida albicans (C. albicans) is an opportunistic pathogen increasingly causing candidiasis worldwide. This study aims to investigate the pattern of systemic immune responses triggered by C. albicans with disease associated variation of Sap2, identifying the novel evasion strategies utilized by clinical isolates. Specifically, a variation in clinical isolates is identified at nucleotide position 817 (G to T). This homozygous variation causes the 273rd amino acid exchange from valine to leucine, close to the proteolytic activation center of Sap2. The mutant (Sap2-273L) generated from SC5314 (Sap2-273V) background carrying the V273L variation within Sap2 displays higher pathogenicity. In comparison to mice infected with Sap2-273V strain, mice infected with Sap2-273L exhibit less complement activation indicated by less serum C3a generation and weaker C3b deposition in the kidney. This inhibitory effect is mainly achieved by Sap2273L -mediated stronger degradation of C3 and C3b. Furthermore, mice infected with Sap2-273L strain exhibit more macrophage phenotype switching from M0 to M2-like and more TGF-β release which further influences T cell responses, generating an immunosuppressed cellular microenvironment characterized by more Tregs and exhausted T cell formation. In summary, the disease-associated sequence variation of Sap2 enhances pathogenicity by complement evasion and M2-like phenotype switching, promoting a more efficient immunosuppressed microenvironment.
Insights
A Candida albicans (C. albicans) variation in Sap2 enhances pathogenicity by evading the immune system. This leads to increased disease severity through complement evasion and altered macrophage responses.
Area of Science:
- Mycology
- Immunology
- Molecular Biology
Background:
- Candida albicans is a major cause of opportunistic fungal infections globally.
- Understanding immune evasion strategies of C. albicans is crucial for treating candidiasis.
Purpose of the Study:
- To investigate immune responses to C. albicans with a specific disease-associated Sap2 variation.
- To identify novel immune evasion mechanisms employed by clinical C. albicans isolates.
Main Methods:
- Generated a mutant Sap2-273L strain from a wild-type Sap2-273V background.
- Infected mice with Sap2-273L and Sap2-273V strains.
- Assessed complement activation (C3a, C3b deposition), macrophage polarization, and T cell responses (Tregs, exhausted T cells).
Main Results:
- The Sap2-273L mutant showed higher pathogenicity than the Sap2-273V strain.
- Sap2-273L exhibited reduced complement activation via enhanced C3 and C3b degradation.
- Infection with Sap2-273L promoted M2-like macrophage polarization and increased TGF-β, leading to immunosuppression with more Tregs and exhausted T cells.
Conclusions:
- A disease-associated Sap2 sequence variation enhances C. albicans pathogenicity.
- This variation promotes immune evasion through complement inhibition and M2-like macrophage polarization.
- The findings reveal mechanisms contributing to an immunosuppressed microenvironment during candidiasis.
