Antifungal Peptides, 2nd Edition

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 8425

Special Issue Editor


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Guest Editor
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40292, USA
Interests: regulation of innate immunity; antimicrobial peptides; antifungal peptides; defensins; cathelicidins; novel antiviral compounds
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Special Issue Information

Dear Colleagues,

Host defense peptides (also called antimicrobial peptides) are ubiquitous in nature, found in all species examined to date. As broad-spectrum antibiotics, they are under intense study to be developed as new antimicrobial agents. Further, their roles in innate host defense are also being studied with an eye toward regulating their expression in order to enhance immunity to infection. In this Issue, we wish to focus on the antifungal activity of these peptides. Of particular interest are studies and reviews on antifungal activities of naturally occurring peptides; synthetic analogues and mimetics of these peptides; regulation of the genes that encode antifungal peptides; their mechanisms of action; and studies on resistance. Studies on emerging fungal pathogens such as Candida auris and on fungal biofilms are especially welcome.

Prof. Dr. Gill Diamond
Guest Editor

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Keywords

  • defensins
  • cathelicidins
  • histatins
  • peptidomimetics
  • cryptides

Published Papers (5 papers)

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Research

15 pages, 14258 KiB  
Article
Exploring Mechanisms of Antifungal Lipopeptide Iturin A from Bacillus against Aspergillus niger
by Shiyi Wang, Min Xu, Ye Han and Zhijiang Zhou
J. Fungi 2024, 10(3), 172; https://doi.org/10.3390/jof10030172 - 24 Feb 2024
Viewed by 1283
Abstract
The control of Aspergillus niger (A. niger) is of great significance for the agricultural economy and food safety. In this study, the antifungal effect and mechanism of iturin A from Bacillus amyloliquefaciens (CGMCC No. 8473) against A. niger (ATCC 16404) were [...] Read more.
The control of Aspergillus niger (A. niger) is of great significance for the agricultural economy and food safety. In this study, the antifungal effect and mechanism of iturin A from Bacillus amyloliquefaciens (CGMCC No. 8473) against A. niger (ATCC 16404) were investigated using biochemical analyses and proteomics. Changes in a mycelium treated with iturin A were observed using scanning electron microscopy and transmission electron microscopy, including mycelial twisting and collapse, organelle disintegration, and intracellular vacuolization. The cytomembrane integrity of A. niger was affected by iturin A, as detected by propidium iodide staining. In addition, the generation of excess reactive oxygen species, the hyperpolarization of the mitochondrial membrane potential and malondialdehyde accumulation also indicated that iturin A induced apoptosis in A. niger through the oxidative stress pathway. Proteomics results showed that 310 proteins were differentially expressed in the A. niger mycelium exposed to iturin A, including 159 upregulated proteins and 151 downregulated proteins, which were mainly associated with energy metabolism of A. niger. We propose that iturin A might inhibit the growth of A. niger by disrupting cytomembrane integrity, via oxidative stress, and by interfering with glycolysis/gluconeogenesis and the tricarboxylic acid cycle. Overall, iturin A is a promising antifungal agent that provides a rationale for controlling A. niger contamination in food. Full article
(This article belongs to the Special Issue Antifungal Peptides, 2nd Edition)
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22 pages, 5876 KiB  
Article
Hyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef1
by Kathy Parisi, James A. McKenna, Rohan Lowe, Karen S. Harris, Thomas Shafee, Rosemary Guarino, Eunice Lee, Nicole L. van der Weerden, Mark R. Bleackley and Marilyn A. Anderson
J. Fungi 2024, 10(1), 54; https://doi.org/10.3390/jof10010054 - 7 Jan 2024
Cited by 2 | Viewed by 1801
Abstract
Plant defensins are a large family of small cationic proteins with diverse functions and mechanisms of action, most of which assert antifungal activity against a broad spectrum of fungi. The partial mechanism of action has been resolved for a small number of members [...] Read more.
Plant defensins are a large family of small cationic proteins with diverse functions and mechanisms of action, most of which assert antifungal activity against a broad spectrum of fungi. The partial mechanism of action has been resolved for a small number of members of plant defensins, and studies have revealed that many act by more than one mechanism. The plant defensin Ppdef1 has a unique sequence and long loop 5 with fungicidal activity against a range of human fungal pathogens, but little is known about its mechanism of action. We screened the S. cerevisiae non-essential gene deletion library and identified the involvement of the mitochondria in the mechanism of action of Ppdef1. Further analysis revealed that the hyperpolarisation of the mitochondrial membrane potential (MMP) activates ROS production, vacuolar fusion and cell death and is an important step in the mechanism of action of Ppdef1, and it is likely that a similar mechanism acts in Trichophyton rubrum. Full article
(This article belongs to the Special Issue Antifungal Peptides, 2nd Edition)
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16 pages, 3594 KiB  
Article
The Plant Defensin Ppdef1 Is a Novel Topical Treatment for Onychomycosis
by Nicole L. van der Weerden, Kathy Parisi, James A. McKenna, Brigitte M. Hayes, Peta J. Harvey, Pedro Quimbar, Sean R. Wevrett, Prem K. Veneer, Owen McCorkelle, Shaily Vasa, Rosemary Guarino, Simon Poon, Yolanda M. Gaspar, Michael J. Baker, David J. Craik, Rob B. Turner, Marc B. Brown, Mark R. Bleackley and Marilyn A. Anderson
J. Fungi 2023, 9(11), 1111; https://doi.org/10.3390/jof9111111 - 17 Nov 2023
Cited by 3 | Viewed by 1632
Abstract
Onychomycosis, or fungal nail infection, causes not only pain and discomfort but can also have psychological and social consequences for the patient. Treatment of onychomycosis is complicated by the location of the infection under the nail plate, meaning that antifungal molecules must either [...] Read more.
Onychomycosis, or fungal nail infection, causes not only pain and discomfort but can also have psychological and social consequences for the patient. Treatment of onychomycosis is complicated by the location of the infection under the nail plate, meaning that antifungal molecules must either penetrate the nail or be applied systemically. Currently, available treatments are limited by their poor nail penetration for topical products or their potential toxicity for systemic products. Plant defensins with potent antifungal activity have the potential to be safe and effective treatments for fungal infections in humans. The cystine-stabilized structure of plant defensins makes them stable to the extremes of pH and temperature as well as digestion by proteases. Here, we describe a novel plant defensin, Ppdef1, as a peptide for the treatment of fungal nail infections. Ppdef1 has potent, fungicidal activity against a range of human fungal pathogens, including Candida spp., Cryptococcus spp., dermatophytes, and non-dermatophytic moulds. In particular, Ppdef1 has excellent activity against dermatophytes that infect skin and nails, including the major etiological agent of onychomycosis Trichophyton rubrum. Ppdef1 also penetrates human nails rapidly and efficiently, making it an excellent candidate for a novel topical treatment of onychomycosis. Full article
(This article belongs to the Special Issue Antifungal Peptides, 2nd Edition)
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14 pages, 3933 KiB  
Article
Small Cationic Cysteine-Rich Defensin-Derived Antifungal Peptide Controls White Mold in Soybean
by Arnaud Thierry Djami-Tchatchou, Meenakshi Tetorya, James Godwin, Jennette M. Codjoe, Hui Li and Dilip M. Shah
J. Fungi 2023, 9(9), 873; https://doi.org/10.3390/jof9090873 - 24 Aug 2023
Cited by 1 | Viewed by 1779
Abstract
White mold disease caused by a necrotrophic ascomycete pathogen Sclerotinia sclerotiorum results in serious economic losses of soybean yield in the USA. Lack of effective genetic resistance to this disease in soybean germplasm and increasing pathogen resistance to fungicides makes white mold difficult [...] Read more.
White mold disease caused by a necrotrophic ascomycete pathogen Sclerotinia sclerotiorum results in serious economic losses of soybean yield in the USA. Lack of effective genetic resistance to this disease in soybean germplasm and increasing pathogen resistance to fungicides makes white mold difficult to manage. Small cysteine-rich antifungal peptides with multi-faceted modes of action possess potential for development as sustainable spray-on bio-fungicides. We have previously reported that GMA4CG_V6 peptide, a 17-amino acid variant of the MtDef4 defensin-derived peptide GMA4CG containing the active γ-core motif, exhibits potent antifungal activity against the gray mold fungal pathogen Botrytis cinerea in vitro and in planta. GMA4CG_V6 exhibited antifungal activity against an aggressive field isolate of S. sclerotiorum 555 in vitro with an MIC value of 24 µM. At this concentration, internalization of this peptide into fungal cells occurred prior to discernible membrane permeabilization. GMA4CG_V6 markedly reduced white mold disease symptoms when applied to detached soybean leaves, pods, and stems. Its spray application on soybean plants provided robust control of this disease. GMA4CG_V6 at sub-lethal concentrations reduced sclerotia production. It was also non-phytotoxic to soybean plants. Our results demonstrate that GMA4CG_V6 peptide has potential for development as a bio-fungicide for white mold control in soybean. Full article
(This article belongs to the Special Issue Antifungal Peptides, 2nd Edition)
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28 pages, 5442 KiB  
Article
Combining the Peptide RWQWRWQWR and an Ethanolic Extract of Bidens pilosa Enhances the Activity against Sensitive and Resistant Candida albicans and C. auris Strains
by Yerly Vargas-Casanova, Claudia Patricia Bravo-Chaucanés, Andrea Ximena Hernández Martínez, Geison Modesti Costa, Jorge Luis Contreras-Herrera, Ricardo Fierro Medina, Zuly Jenny Rivera-Monroy, Javier Eduardo García-Castañeda and Claudia Marcela Parra-Giraldo
J. Fungi 2023, 9(8), 817; https://doi.org/10.3390/jof9080817 - 2 Aug 2023
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Abstract
The antifungal activity of palindromic peptide RWQWRWQWR and its derivatives was evaluated against clinical isolates of Candida albicans and C. auris. Also, Bidens pilosa ethanolic extracts of leaves and stem were evaluated. Furthermore, combinations of peptide, extract, and/or fluconazole (FLC) were evaluated. [...] Read more.
The antifungal activity of palindromic peptide RWQWRWQWR and its derivatives was evaluated against clinical isolates of Candida albicans and C. auris. Also, Bidens pilosa ethanolic extracts of leaves and stem were evaluated. Furthermore, combinations of peptide, extract, and/or fluconazole (FLC) were evaluated. The cytotoxicity of peptides and extracts in erythrocytes and fibroblasts was determined. The original palindromic peptide, some derivative peptides, and the ethanolic extract of leaves of B. pilosa exhibited the highest activity in some of the strains evaluated. Synergy was obtained between the peptide and the FLC against C. auris 435. The combination of the extract and the original palindromic peptide against C. albicans SC5314, C. auris 435, and C. auris 537 decreased the minimal inhibitory concentrations (MICs) by a factor of between 4 and 16. These mixtures induced changes in cell morphology, such as deformations on the cell surface. The results suggest that the combination of RWQWRWQWR and B. pilosa extract is an alternative for enhancing antifungal activity and decreasing cytotoxicity and costs and should be considered to be a promising strategy for treating diseases caused by Candida spp. Full article
(This article belongs to the Special Issue Antifungal Peptides, 2nd Edition)
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