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Candida parapsilosis Cell Wall Proteome Characterization and Effectiveness against Hematogenously Disseminated
Xiaolong Gong1, Vartika Srivastava1, Previn Naicker2
1Clinical Microbiology and Infectious Diseases, School of Pathology, Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Abstract:
Candida parapsilosis poses huge treatment challenges in the clinical settings of South Africa, and often causes infections among immunocompromised patients and underweight neonates. Cell wall proteins have been known to play vital roles in fungal pathogenesis, as these are the first points of contact toward environments, the host, and the immune system. This study characterized the cell wall immunodominant proteins of pathogenic yeast C. parapsilosis and evaluated their protective effects in mice, which could add value in vaccine development against the rising C. parapsilosis infections. Among different clinical strains, the most pathogenic and multidrug-resistant C. parapsilosis isolate was selected based on their susceptibility towards antifungal drugs, proteinase, and phospholipase secretions. Cell wall antigens were prepared by β-mercaptoethanol/ammonium bicarbonate extraction from selected C. parapsilosis strains. Antigenic proteins were identified using LC-MS/MS, where 933 proteins were found, with 34 being immunodominant. The protective effect of the cell wall immunodominant proteins was observed by immunizing BALB/c mice with cell wall protein extracts. After the immunization and booster, the BALC/c mice were challenged with a lethal dose of C. parapsilosis. In vivo results demonstrated increased survival rates and lower fungal burden in vital organs in the immunized mice compared to the unimmunized mice, thereby confirming the immunogenic property of cell wall-associated proteins of C. parapsilosis. Therefore, these results advocated the potential of these cell wall proteins to act as biomarkers for the development of diagnostic assays and/or vaccines against infections caused by C. parapsilosis.
Insights
This study identified key cell wall proteins from Candida parapsilosis that show protective effects against infection in mice. These findings support the development of new vaccines and diagnostic tools for this challenging fungal pathogen.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Candida parapsilosis causes significant clinical challenges, particularly in South Africa, affecting immunocompromised individuals and neonates.
- Fungal cell wall proteins are crucial for pathogenesis, mediating interactions with the host and immune system.
Purpose of the Study:
- To characterize immunodominant cell wall proteins of pathogenic Candida parapsilosis.
- To evaluate the protective potential of these proteins in a murine model for vaccine development.
Main Methods:
- Selected the most pathogenic and multidrug-resistant C. parapsilosis strains.
- Extracted cell wall antigens using a β-mercaptoethanol/ammonium bicarbonate method.
- Identified antigenic proteins via LC-MS/MS and assessed immunogenicity in BALB/c mice.
Main Results:
- Identified 933 proteins, with 34 designated as immunodominant.
- Immunized mice with cell wall protein extracts showed increased survival rates.
- Vaccinated mice exhibited a reduced fungal burden in vital organs post-challenge.
Conclusions:
- Cell wall-associated proteins of C. parapsilosis possess immunogenic properties.
- These proteins show potential as biomarkers for developing diagnostic assays.
- The identified proteins could be valuable for creating novel vaccines against C. parapsilosis infections.
