Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB

• Published in: Biochimica et biophysica acta. Biomembranes Vol. 1862; no. 8; p. 183246
• Main Authors: Huber, A., Galgóczy, L., Váradi, G., Holzknecht, J., Kakar, A., Malanovic, N., Leber, R., Koch, J., Keller, M.A., Batta, G., Tóth, G.K., Marx, F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2020; The Author(s). Published by Elsevier B.V
• Subjects: Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial proteins and peptides; Apoptosis; Apoptosis - drug effects; Cell Membrane - drug effects; Cysteine - genetics; Endocytosis; Fungal membrane lipids; Fungal Proteins - chemistry; Fungal Proteins - genetics; Humans; Membrane Lipids - chemistry; Mycoses - drug therapy; Mycoses - genetics; Mycoses - microbiology; Penicillium chrysogenum; Penicillium chrysogenum - chemistry; Penicillium chrysogenum - genetics; β-Fold structure; γ-Core; Antimicrobial proteins and peptides; β-Fold structure; Endocytosis; Fungal membrane lipids; γ-Core; Penicillium chrysogenum; Apoptosis
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2020.183246

The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, β-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo.
The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution.
In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics.
[Display omitted]
•Penicillium chrysogenum secretes the small, cysteine-rich proteins PAF and PAFB.•Both exhibit antifungal activity, but with differences in their mode of action.•Structure, membrane interaction and cellular uptake determine their function.•PAF and PAFB are well tolerated by mammalian cells.•They promise applicability in medicine, plant protection and food industry.