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Gradual solubilization of Candida cell wall beta-glucan by oxidative degradation in mice
1Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Abstract:
Candida spp. is a medically important fungi which induces disseminated candidiasis and candidemia in hospitalized immunocompromised patients. The cell wall of Candida is mainly composed of two polysaccharides, mannan and beta-glucan, and at least part of beta-glucan is basically insoluble in H2O or NaOH. We became interested in when and how particulate beta-glucan changes to the soluble form. However, the fate of wall components has not been examined in detail. In this study, modification and solubilization of the cell wall beta-glucan were analyzed in vivo and in vitro. Cells of Candida, intravenously administered to mice (1 mg/mouse), were immediately deposited mainly in liver as determined by 3H-labeled cells. Beta-Glucans were detected in these mice for at least for 6 months by the beta-glucan specific assay. During this period, the insoluble cell wall beta-glucan was gradually solubilized in these organs, probably by oxidative stress of macrophages. Candida cells and particulate beta-glucans were also gradually solubilized in vitro using sodium hypochlorite solution, but part of the cell wall beta-glucan was still insoluble even after treatment with concentrated hypochlorite solution for one day at room temperature. These findings strongly suggested that the fungal cell wall beta-glucans were quite resistant to oxidative metabolism in vivo and in vitro, and thus deposited for quite long period in the host.
Insights
The fungal cell wall component beta-glucan is gradually solubilized in the host over months, likely due to macrophage oxidative stress. However, Candida beta-glucans show significant resistance to degradation, persisting in the host for extended periods.
Area of Science:
- Mycology
- Immunology
- Biochemistry
Background:
- Candida spp. are medically significant fungi causing candidiasis and candidemia in immunocompromised patients.
- The Candida cell wall comprises mannan and beta-glucan polysaccharides, with partially insoluble beta-glucan.
- The transformation and fate of insoluble beta-glucan in vivo remain underexplored.
Purpose of the Study:
- To investigate the modification and solubilization of Candida cell wall beta-glucan.
- To determine the in vivo and in vitro fate of insoluble beta-glucan.
Main Methods:
- Intravenous administration of 3H-labeled Candida cells to mice.
- Detection of beta-glucans in host organs over time using a specific assay.
- In vitro solubilization assays using sodium hypochlorite solution.
Main Results:
- Insoluble cell wall beta-glucan was gradually solubilized in mouse liver over 6 months, likely via macrophage oxidative stress.
- Candida cells and particulate beta-glucans showed gradual solubilization in vitro with sodium hypochlorite.
- A portion of cell wall beta-glucan remained insoluble even after prolonged exposure to concentrated hypochlorite.
Conclusions:
- Candida cell wall beta-glucans exhibit considerable resistance to host oxidative metabolism.
- Insoluble beta-glucans can persist in host tissues for extended durations.
- Understanding beta-glucan resistance is crucial for managing Candida infections.