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Antifungal activity of cerebrospinal fluid against Cryptococcus neoformans and Candida species
E Brummer1, T Drasin, J D Adler
1Division of Infectious Diseass, Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA. E.Brummer@Juno.com
Abstract:
The effect of human cerebrospinal fluid (CSF) on the growth of Cryptococcus neoformans and Candida species was tested in RPMI-1640. CSF alone was highly fungistatic for both yeasts and inhibited growth in a concentration-dependent manner. Unlike human serum, CSF did not collaborate with fluconazole for killing C. neoformans. Molecular sieve fractionation of CSF on a G-200 Sephadex column yielded a highly antifungal fraction with a molecular weight around 66 kDa. On SDS-PAGE this fraction migrated as a major and a minor band corresponding to the mobility of bovine serum albumin. These novel findings suggest that CSF contains a factor(s) that provides resistance to the growth of C. neoformans or Candida species.
Insights
Human cerebrospinal fluid (CSF) inhibits the growth of Cryptococcus neoformans and Candida species. A specific protein fraction in CSF, similar to bovine serum albumin, demonstrates potent antifungal activity.
Area of Science:
- Mycology
- Infectious Diseases
- Biochemistry
Background:
- Cryptococcus neoformans and Candida species are significant fungal pathogens.
- The human cerebrospinal fluid (CSF) role in controlling these infections is not fully understood.
- Antifungal resistance mechanisms in the central nervous system require further investigation.
Purpose of the Study:
- To investigate the effect of human cerebrospinal fluid (CSF) on the in vitro growth of Cryptococcus neoformans and Candida species.
- To identify potential antifungal factors within the CSF.
- To compare the antifungal properties of CSF with human serum.
Main Methods:
- Yeast growth inhibition assays were performed using RPMI-1640 medium supplemented with varying concentrations of human CSF.
- Synergistic effects of CSF and fluconazole were evaluated for Cryptococcus neoformans.
- Molecular sieve fractionation (G-200 Sephadex) and SDS-PAGE were employed to isolate and characterize antifungal components in CSF.
Main Results:
- Human CSF demonstrated significant fungistatic activity against both C. neoformans and Candida species in a concentration-dependent manner.
- CSF did not exhibit synergistic antifungal activity with fluconazole against C. neoformans, unlike human serum.
- A major antifungal fraction was isolated from CSF with an approximate molecular weight of 66 kDa, identified as similar to bovine serum albumin.
Conclusions:
- Human CSF possesses intrinsic fungistatic properties against common fungal pathogens.
- A protein factor, likely albumin, in CSF contributes significantly to its antifungal activity.
- These findings suggest a novel host defense mechanism within the central nervous system against fungal infections.