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Characterization of an anticryptococcal protein isolated from human serum
S Sridhar1, M Ahluwalia, E Brummer
1Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, and California Institute for Medical Research, San Jose, California, USA.
Infection and Immunity
|May 19, 2000
Summary
Human serum inhibits Cryptococcus neoformans growth. This effect is attributed to transferrin, a protein whose inhibitory action is reversed by iron (FeCl3).
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Human serum exhibits antimicrobial properties against various pathogens.
- Cryptococcus neoformans is an opportunistic fungal pathogen causing serious infections, particularly in immunocompromised individuals.
- The specific components within serum responsible for inhibiting C. neoformans growth require further elucidation.
Purpose of the Study:
- To identify and characterize the serum protein responsible for inhibiting Cryptococcus neoformans growth in vitro.
- To investigate the mechanism underlying the inhibitory activity of this protein.
Main Methods:
- Fractionation of human serum to isolate the inhibitory component.
- Biochemical characterization of the purified protein, including molecular mass and isoelectric point determination.
- Amino acid sequencing to identify the protein.
- In vitro growth inhibition assays of C. neoformans with purified protein, apotransferrin, and human serum, assessing the effect of iron supplementation.
Main Results:
- A protein with a molecular mass of approximately 81.8 kDa and a pI of 6.2 was purified from human serum.
- The amino acid sequence of the purified protein matched human transferrin.
- The inhibitory activity of transferrin, apotransferrin, and 5% human serum against C. neoformans was reversed by the addition of ferric chloride (FeCl3).
Conclusions:
- Human transferrin is a key component of serum that inhibits the in vitro growth of Cryptococcus neoformans.
- The iron-binding capacity of transferrin appears crucial for its antifungal activity, suggesting iron sequestration as a potential mechanism.
- These findings highlight transferrin's role in innate immunity against fungal infections and suggest potential therapeutic strategies targeting iron availability.