β-Microseminoprotein Endows Post Coital Seminal Plasma with Potent Candidacidal Activity by a Calcium- and pH-Dependent Mechanism

PLoS Pathogens

Alexander M. Cole¹  Martin Malmsten²  Per Fernlund³  Victoria Rydengård⁴  Ole E. Sørensen⁵  Anneli M. L. Edström Hägerwall⁵  Matthias Mörgelin⁵  Maria Baumgarten⁵  Birthe B. Kragelund⁶ 

[1] Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, United States of America;Department of Pharmacy, Uppsala University, Uppsala, Sweden;Division of Clinical Chemistry, Department of Laboratory Medicine Malmö, Lund University, Malmö, Sweden;Division of Dermatology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Copenhagen, Denmark

关键词: Antifungals;    Fungicides;    C;    ida albicans;    Fungal structure;    Liposomes;    C;    ida;    Blood plasma;    Copulation;   

DOI  :  10.1371/journal.ppat.1002625

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The innate immune factors controlling Candida albicans are mostly unknown. Vulvovaginal candidiasis is common in women and affects approximately 70–75% of all women at least once. Despite the propensity of Candida to colonize the vagina, transmission of Candida albicans following sexual intercourse is very rare. This prompted us to investigate whether the post coital vaginal milieu contained factors active against C. albicans. By CFU assays, we found prominent candidacidal activity of post coital seminal plasma at both neutral and the acid vaginal pH. In contrast, normal seminal plasma did not display candidacidal activity prior to acidification. By antifungal gel overlay assay, one clearing zone corresponding to a protein band was found in both post coital and normal seminal plasma, which was subsequently identified as β-microseminoprotein. At neutral pH, the fungicidal activity of β-microseminoprotein and seminal plasma was inhibited by calcium. By NMR spectroscopy, amino acid residue E71 was shown to be critical for the calcium coordination. The acidic vaginal milieu unleashed the fungicidal activity by decreasing the inhibitory effect of calcium. The candidacidal activity of β-microseminoprotein was mapped to a fragment of the C-terminal domain with no structural similarity to other known proteins. A homologous fragment from porcine β-microseminoprotein demonstrated calcium-dependent fungicidal activity in a CFU assay, suggesting this may be a common feature for members of the β-microseminoprotein family. By electron microscopy, β-microseminoprotein was found to cause lysis of Candida. Liposome experiments demonstrated that β-microseminoprotein was active towards ergosterol-containing liposomes that mimic fungal membranes, offering an explanation for the selectivity against fungi. These data identify β-microseminoprotein as an important innate immune factor active against C. albicans and may help explain the low sexual transmission rate of Candida.

【 授权许可】

CC BY