Authors

Amle Hagerwall; V. Rydengard; P. Fernlund; M. Morgelin; M. Baumgarten; A. M. Cole; M. Malmsten; B. B. Kragelund;O. E. Sorensen

Comments

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Abbreviated Journal Title

PLoS Pathog.

Keywords

PROSTATE SECRETORY PROTEIN; ANTIMICROBIAL PEPTIDES; VAGINAL CANDIDIASIS; TUMOR-GROWTH; HUMAN-SEMEN; HYPERCALCEMIA; MALIGNANCY; HCAP-18; LL-37; Microbiology; Parasitology; Virology

Abstract

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 beta-microseminoprotein. At neutral pH, the fungicidal activity of beta-microseminoprotein and seminal plasma was inhibited by calcium. By NMR spectroscopy, amino acid residue E-71 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 beta-microseminoprotein was mapped to a fragment of the C-terminal domain with no structural similarity to other known proteins. A homologous fragment from porcine beta-microseminoprotein demonstrated calcium-dependent fungicidal activity in a CFU assay, suggesting this may be a common feature for members of the beta-microseminoprotein family. By electron microscopy, beta-microseminoprotein was found to cause lysis of Candida. Liposome experiments demonstrated that beta-microseminoprotein was active towards ergosterol-containing liposomes that mimic fungal membranes, offering an explanation for the selectivity against fungi. These data identify beta-microseminoprotein as an important innate immune factor active against C. albicans and may help explain the low sexual transmission rate of Candida.

Journal Title

Plos Pathogens

Volume

8

Issue/Number

4

Publication Date

1-1-2012

Document Type

Article

Language

English

First Page

12

WOS Identifier

WOS:000303444200021

ISSN

1553-7374

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