As a consequence of emerging numbers of vulvovaginitis cases caused by azole-resistant
and biofilm-forming Candida species, 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,
Neosartorya fischeri antifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a
fluconazole (FLC)-resistant Candida albicans strain isolated from a 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 MIC in vitro. In vivo murine vulvovaginitis model experiments
showed that NFAP2 significantly decreases the number of FLC-resistant C. albicans
cells, 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.
