In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis

As a consequence of emerging numbers of vulvovaginitis cases caused by azole-resistant and biofilm-forming 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 recur...

Full description

Saved in:
Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2019-02, Vol.63 (2)
Main Authors: Kovács, Renátó, Holzknecht, Jeanett, Hargitai, Zoltán, Papp, Csaba, Farkas, Attila, Borics, Attila, Tóth, Lilána, Váradi, Györgyi, Tóth, Gábor K, Kovács, Ilona, Dubrac, Sandrine, Majoros, László, Marx, Florentine, Galgóczy, László
Format: Article
Language:English
Subjects:
Animals
Antifungal Agents
Antifungal Agents - metabolism
Antifungal Agents - therapeutic use
Candidiasis, Vulvovaginal
Candidiasis, Vulvovaginal - drug therapy
Candidiasis, Vulvovaginal - microbiology
Drug Resistance, Fungal
Experimental Therapeutics
Female
Flow Cytometry
Humans
Mice
Mice, Inbred BALB C
Microbial Sensitivity Tests
Neosartorya
Neosartorya - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:As a consequence of emerging numbers of vulvovaginitis cases caused by azole-resistant and biofilm-forming 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 spp. ; however, no information is available about their 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, antifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a fluconazole (FLC)-resistant strain isolated from a vulvovaginal infection, and it was effective against both planktonic cells and biofilm 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 murine vulvovaginitis model experiments showed that NFAP2 significantly decreases the number of FLC-resistant 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.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.01777-18