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 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.
Highlights
Innate immunity plays a major role in the host defense against Candida albicans infections, the specific innate immune factors controlling Candida are unknown [1]
Since Candida is rarely transmitted by vaginal intercourse, we investigated the activity of post coital seminal plasma collected as a post coital vaginal aspirate 8–10 hours after sexual intercourse
Penile-vaginal transmission of Candida is rare [2]. This difference between the sexual transmission of bacterial vaginosis and vaginal candidiasis is quite remarkable since seminal plasma contains potent antibacterial activity [4,5,6,7]
Summary
Innate immunity plays a major role in the host defense against Candida albicans infections, the specific innate immune factors controlling Candida are unknown [1]. While frequent sexual intercourse is associated with bacterial vaginosis, this is not the case with vaginal candidiasis [3] despite the propensity of Candida to colonize the vagina This difference between sexual transmission of bacterial vaginosis and vaginal candidiasis is striking since seminal plasma contains potent antibacterial activity [4,5,6,7] playing a role in limiting bacterial proliferation after sexual intercourse. Despite the fact that human seminal plasma contains potent antibacterial and antiviral activity [4,6,7,8], we found no studies describing significant antifungal activity of seminal plasma or vaginal fluid against Candida.
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