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Article

The Penicillium chrysogenum Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen Candida albicans

by
Jeanett Holzknecht
1,
Alexander Kühbacher
1,
Csaba Papp
2,
Attila Farkas
3,
Györgyi Váradi
4,
Jose F. Marcos
5,
Paloma Manzanares
5,
Gábor K. Tóth
4,6,
László Galgóczy
3,7,* and
Florentine Marx
1,*
1
Biocenter, Institute of Molecular Biology, Medical University of Innsbruck, Innrain 80–82, A-6020 Innsbruck, Austria
2
Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary
3
Institute of Plant Biology, Biological Research Centre, Temesvári krt. 62, H-6726 Szeged, Hungary
4
Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary
5
Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Consejo Superior de Investigaciones Científicas (CSIC), Paterna, E-46980 Valencia, Spain
6
MTA-SZTE Biomimetic Systems Research Group, University of Szeged, Dóm tér 8, H-6726 Szeged, Hungary
7
Department of Biotechnology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary
*
Authors to whom correspondence should be addressed.
J. Fungi 2020, 6(3), 141; https://doi.org/10.3390/jof6030141
Submission received: 10 July 2020 / Revised: 6 August 2020 / Accepted: 11 August 2020 / Published: 19 August 2020
(This article belongs to the Special Issue Antifungal Peptides 2020)
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Abstract

Small, cysteine-rich and cationic antimicrobial proteins (AMPs) from filamentous ascomycetes promise treatment alternatives to licensed antifungal drugs. In this study, we characterized the Penicillium chrysogenum Q176 antifungal protein C (PAFC), which is phylogenetically distinct to the other two Penicillium antifungal proteins, PAF and PAFB, that are expressed by this biotechnologically important ascomycete. PAFC is secreted into the culture broth and is co-expressed with PAF and PAFB in the exudates of surface cultures. This observation is in line with the suggested role of AMPs in the adaptive response of the host to endogenous and/or environmental stimuli. The in silico structural model predicted five β-strands stabilized by four intramolecular disulfide bonds in PAFC. The functional characterization of recombinant PAFC provided evidence for a promising new molecule in anti-Candida therapy. The thermotolerant PAFC killed planktonic cells and reduced the metabolic activity of sessile cells in pre-established biofilms of two Candidaalbicans strains, one of which was a fluconazole-resistant clinical isolate showing higher PAFC sensitivity than the fluconazole-sensitive strain. Candidacidal activity was linked to severe cell morphology changes, PAFC internalization, induction of intracellular reactive oxygen species and plasma membrane disintegration. The lack of hemolytic activity further corroborates the potential applicability of PAFC in clinical therapy.
Keywords: Penicillium chrysogenum antimicrobial protein C; PAFC; exudate; Candida albicans; reactive oxygen species; plasma membrane permeabilization; cell death Penicillium chrysogenum antimicrobial protein C; PAFC; exudate; Candida albicans; reactive oxygen species; plasma membrane permeabilization; cell death

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MDPI and ACS Style

Holzknecht, J.; Kühbacher, A.; Papp, C.; Farkas, A.; Váradi, G.; Marcos, J.F.; Manzanares, P.; Tóth, G.K.; Galgóczy, L.; Marx, F. The Penicillium chrysogenum Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen Candida albicans. J. Fungi 2020, 6, 141. https://doi.org/10.3390/jof6030141

AMA Style

Holzknecht J, Kühbacher A, Papp C, Farkas A, Váradi G, Marcos JF, Manzanares P, Tóth GK, Galgóczy L, Marx F. The Penicillium chrysogenum Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen Candida albicans. Journal of Fungi. 2020; 6(3):141. https://doi.org/10.3390/jof6030141

Chicago/Turabian Style

Holzknecht, Jeanett, Alexander Kühbacher, Csaba Papp, Attila Farkas, Györgyi Váradi, Jose F. Marcos, Paloma Manzanares, Gábor K. Tóth, László Galgóczy, and Florentine Marx. 2020. "The Penicillium chrysogenum Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen Candida albicans" Journal of Fungi 6, no. 3: 141. https://doi.org/10.3390/jof6030141

APA Style

Holzknecht, J., Kühbacher, A., Papp, C., Farkas, A., Váradi, G., Marcos, J. F., Manzanares, P., Tóth, G. K., Galgóczy, L., & Marx, F. (2020). The Penicillium chrysogenum Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen Candida albicans. Journal of Fungi, 6(3), 141. https://doi.org/10.3390/jof6030141

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