In vivo applicability of Neosartorya fischeri antifungal protein 2 (NFAP2) in treatment of vulvovaginal candidiasis [Experimental Therapeutics]

In the consequence of emerging number of vulvovaginitis caused by azole-resistant and biofilm-forming Candida species, the fast and efficient treatment of this infection has become challenging. The problem is further exacerbated by the severe side-effects of azoles as long-term use medications in the recurrent form. There is therefore an increasing demand for novel and safely applicable effective antifungal therapeutic strategies. The small, cysteine-rich and cationic antifungal proteins from filamentous ascomycetes are potential candidates as they inhibit the growth of several Candida spp. in vitro; however no information is available about their in vivo antifungal potency against yeasts. In the present study we investigated the possible therapeutic application of one of their representatives in the treatment of vulvovaginal candidiasis, the Neosartorya fischeri antifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a fluconazole (FLC)-resistant Candida albicans strain isolated from vulvovaginal infection, and it was effective against both planktonic cells and biofilm in vitro. We observed that the fungal cell killing activity of NFAP2 is connected to its pore-forming ability in the cell membrane. NFAP2 did not exert cytotoxic effects on primary human keratinocytes and dermal fibroblasts at the minimal inhibitory concentration in vitro. In vivo murine vulvovaginitis model experiments showed that NFAP2 significantly decreases the cell number of the FLC-resistant C. albicans, and the combined application with FLC enhances the efficacy. These results suggest that NFAP2 provides a feasible base for the development of a fundamental new, safely applicable mono- or polytherapeutic topical agent in the treatment of superficial candidiasis.

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