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

Renátó Kovács, Jeanett Holzknecht, Zoltán Hargitai, Csaba Papp, Attila Farkas, Attila Borics, Lilána Tóth, Györgyi Váradi, G. Tóth, I. Kovács, Sandrine Dubrac, László Majoros, Florentine Marx, László Galgóczy

Research output: Article

Abstract

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.

Original languageEnglish
Article numbere01777-18
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number2
DOIs
Publication statusPublished - febr. 1 2019

Fingerprint

Neosartorya
Vulvovaginal Candidiasis
Fluconazole
Vulvovaginitis
Proteins
Azoles
Biofilms
Candida albicans
Candida
Ascomycota
Candidiasis
Growth
Infection
Keratinocytes
Cysteine
Fibroblasts
Yeasts
Cell Membrane
Skin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Kovács, R., Holzknecht, J., Hargitai, Z., Papp, C., Farkas, A., Borics, A., ... Galgóczy, L. (2019). In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis. Antimicrobial Agents and Chemotherapy, 63(2), [e01777-18]. https://doi.org/10.1128/AAC.01777-18

In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis. / Kovács, Renátó; Holzknecht, Jeanett; Hargitai, Zoltán; Papp, Csaba; Farkas, Attila; Borics, Attila; Tóth, Lilána; Váradi, Györgyi; Tóth, G.; Kovács, I.; Dubrac, Sandrine; Majoros, László; Marx, Florentine; Galgóczy, László.

In: Antimicrobial Agents and Chemotherapy, Vol. 63, No. 2, e01777-18, 01.02.2019.

Research output: Article

Kovács, R, Holzknecht, J, Hargitai, Z, Papp, C, Farkas, A, Borics, A, Tóth, L, Váradi, G, Tóth, G, Kovács, I, Dubrac, S, Majoros, L, Marx, F & Galgóczy, L 2019, 'In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis', Antimicrobial Agents and Chemotherapy, vol. 63, no. 2, e01777-18. https://doi.org/10.1128/AAC.01777-18
Kovács, Renátó ; Holzknecht, Jeanett ; Hargitai, Zoltán ; Papp, Csaba ; Farkas, Attila ; Borics, Attila ; Tóth, Lilána ; Váradi, Györgyi ; Tóth, G. ; Kovács, I. ; Dubrac, Sandrine ; Majoros, László ; Marx, Florentine ; Galgóczy, László. / In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis. In: Antimicrobial Agents and Chemotherapy. 2019 ; Vol. 63, No. 2.
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