In VivoApplicability ofNeosartorya fischeriAntifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis
ABSTRACTAs a consequence of emerging numbers of vulvovaginitis cases caused by azole-resistant and biofilm-formingCandidaspecies, 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 severalCandidaspp.in vitro; however, no information is available about theirin vivoantifungal potency against yeasts. In the present study, we investigated the possible therapeutic application of one of their representatives in the treatment of vulvovaginal candidiasis,Neosartorya fischeriantifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a fluconazole (FLC)-resistantCandida albicansstrain isolated from a vulvovaginal infection, and it was effective against both planktonic cells and biofilmin 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 MICin vitro. In vivomurine vulvovaginitis model experiments showed that NFAP2 significantly decreases the number of FLC-resistantC. albicanscells, and 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 for the treatment of superficial candidiasis.