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Alternative Therapeutic Approaches of Candida Infections, 4th Edition
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Alternative Therapeutic Approaches of Candida Infections, 4th Edition

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: 31 August 2026 | Viewed by 8071

Special Issue Editor

Dr. Renátó Kovács

E-Mail Website
Guest Editor
Faculty of Medicine, Department of Medical Microbiology, University of Debrecen, Debrecen, Hungary
Interests: biofilms; quorum-sensing; antifungal drugs; clinical mycology; alternative therapies; Candida spp.; fungal–bacterial interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Candida infections are considered a serious public health problem worldwide, especially in immunocompromised patient populations. In addition, the morbidity and mortality rate associated with these infections have not improved significantly over the past few years. The prevalence and incidence of infections caused by Candida species resistant to one or more first-line antifungals has been steadily increasing due to the widespread use of antifungal drugs in agriculture and both veterinary and human medicine. Moreover, biofilm production plays a pivotal role in resistance to traditional antifungals, restricting the proper choice of therapy. As the available antifungal agents are decreasing in efficacy, new innovative approaches have to be implemented in the future in order to eradicate these infections. Alternative therapies involve the administration of combination-based therapies, the usage of antifungal peptides and proteins, plant extracts or natural products, therapies disrupting quorum-sensing, and photodynamic therapy.

Dr. Renátó Kovács
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Candida
  • in vitro and in vivo susceptibility
  • therapy
  • biofilms
  • combination
  • antifungals
  • quorum-sensing
  • natural products
  • antifungal peptides and proteins
  • photodynamic therapy
  • resistance
  • synergy
  • Candida auris
  • fluconazole-resistant Candida species
  • echinocandin resistance

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Related Special Issue

Published Papers (5 papers)

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Research

16 pages, 2241 KB  
Article
A Carboxyl-Functionalized Graphene Quantum Dot Coating for Catheters Effective Against Emerging Drug-Resistant Candidozyma auris
by Laure S. van Hofwegen, Muhammad Hassnain, Payal P. S. Balraadjsing, Karin van Dijk, Ferry Hagen, Sedat Nizamoglu and Sebastian A. J. Zaat
J. Fungi 2026, 12(3), 216; https://doi.org/10.3390/jof12030216 - 17 Mar 2026
Viewed by 499
Abstract
Candidozyma auris is an emerging opportunistic fungal pathogen that can cause serious catheter-related blood stream infections associated with high morbidity and mortality. The traditional antifungal treatment with polyenes, azoles or echinocandins is becoming less effective due to both intrinsic and developed resistance, complicating [...] Read more.
Candidozyma auris is an emerging opportunistic fungal pathogen that can cause serious catheter-related blood stream infections associated with high morbidity and mortality. The traditional antifungal treatment with polyenes, azoles or echinocandins is becoming less effective due to both intrinsic and developed resistance, complicating treatment. This study demonstrates the potent fungicidal activity of carboxyl-functionalized graphene quantum dots (cGQDs) against a panel of C. auris strains, spanning clades I to V, and a Candida albicans reference strain. Photoactivation of cGQDs in suspension with 435 nm blue light killed 99.9% of the fungi within 30 min even though the majority of test strains were resistant to at least one conventional antifungal. Moreover, cGQDs coated on flexible polydimethylsiloxane surfaces and commercial catheters via electrostatic layer-by-layer deposition with alternating positively charged polydiallyldimethylammonium polymer showed strong fungicidal activity against C. auris and C. albicans. These findings show that the cGQDs, both in suspension and in a thin film coating, have potential for future clinical development. In particular, their application to catheters may help prevent Candidozyma and Candida catheter-related infections. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 4th Edition)
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22 pages, 7601 KB  
Article
Amphibian-Derived Peptide Analog TB_KKG6K: A Powerful Drug Candidate Against Candida albicans with Anti-Biofilm Efficacy
by Cristina Schöpf, Anik Geschwindt, Magdalena Knapp, Anna C. Seybold, Débora C. Coraça-Huber, Michael J. Ausserlechner, Alessandra Romanelli and Florentine Marx
J. Fungi 2026, 12(1), 11; https://doi.org/10.3390/jof12010011 - 23 Dec 2025
Viewed by 619
Abstract
Candida albicans, a commensal and opportunistic fungal pathogen, is a major clinical concern due to its ability to cause infections ranging from mild mucosal conditions to life-threatening systemic diseases, particularly in immunocompromised patients. Its capacity to form biofilms on medical devices further [...] Read more.
Candida albicans, a commensal and opportunistic fungal pathogen, is a major clinical concern due to its ability to cause infections ranging from mild mucosal conditions to life-threatening systemic diseases, particularly in immunocompromised patients. Its capacity to form biofilms on medical devices further complicates treatment by enhancing antifungal resistance and immune evasion. In the search for novel therapeutic strategies, the lysine-enriched amphibian-derived temporin B analog, TB_KKG6K, has emerged as a promising antifungal agent. This study demonstrates that TB_KKG6K exhibits potent fungicidal activity against planktonic C. albicans cells, with a low potential to induce adaptation or resistance. TB_KKG6K has no adverse impact on the anti-Candida efficacy of standard antifungal drugs when applied in combination, interacting additively with amphotericin B and caspofungin in a fungicidal mode of action. Additionally, TB_KKG6K effectively reduces biofilm maturation on silicone elastomers, a material commonly used in medical devices, further highlighting its therapeutic potential. These data together with our previous documentation of minimal cytotoxicity and irritation potential in human cells makes TB_KKG6K a strong candidate for combating both planktonic and biofilm-associated C. albicans infections. These findings underscore the dual efficacy of TB_KKG6K and its potential to address the challenges posed by C. albicans in clinical settings. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 4th Edition)
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14 pages, 2383 KB  
Article
Myricetin Exerts Antibiofilm Effects on Candida albicans by Targeting the RAS1/cAMP/EFG1 Pathway and Disruption of the Hyphal Network
by Melda Meral Ocal, Merve Aydin, Esra Sumlu, Emine Nedime Korucu and Ali Ozturk
J. Fungi 2025, 11(5), 398; https://doi.org/10.3390/jof11050398 - 21 May 2025
Cited by 3 | Viewed by 1919
Abstract
Increasing antifungal resistance and side effects of existing drugs demand alternative approaches for treating Candida (C.) infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both fluconazole (FLC)-resistant and susceptible clinical Candida strains, [...] Read more.
Increasing antifungal resistance and side effects of existing drugs demand alternative approaches for treating Candida (C.) infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both fluconazole (FLC)-resistant and susceptible clinical Candida strains, with a particular focus on its inhibitory effects on C. albicans biofilms. Antifungal susceptibility was evaluated on Candida spp. by the broth microdilution method, and the impact of myricetin on C. albicans biofilms was determined using the Cell Counting Kit-8 (CCK-8) assay. To understand the molecular mechanisms underlying the antibiofilm properties of myricetin, expression analysis of genes in the RAS1/cAMP/EFG1 pathway (ALS3, HWP1, ECE1, UME6, HGC1) and cAMP-dependent protein kinase regulation (RAS1, CYR1, EFG1) involved in the transition from yeast to hyphae was performed. Field emission scanning electron microscopy (FESEM) was used to study the ultrastructural changes and morphological dynamics of Candida biofilms after exposure to MYR and FLC. The in vivo toxicity of myricetin was evaluated by survival analysis using the Galleria mellonella model. Myricetin significantly suppressed key genes related to hyphae development (RAS1, CYR1, EFG1, UME6, and HGC1) and adhesion (ALS3 and HWP1) in both clinical and reference Candida strains at a concentration of 640 µg/mL. FESEM analysis revealed that myricetin inhibited hyphae growth and elongation in C. albicans. This study highlights the promising antibiofilm potential of myricetin through a significant inhibition of biofilm formation and hyphal morphogenesis. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 4th Edition)
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28 pages, 5232 KB  
Article
Evaluation of the Synergistic Activity of Antimicrobial Peptidomimetics or Colistin Sulphate with Conventional Antifungals Against Yeasts of Medical Importance
by Shyam Kumar Mishra, Rajesh Kuppusamy, Christina Nguyen, Jennifer Doeur, Harleen Atwal, Samuel Attard, Kristian Sørensen, Jennifer S. Lin, Edgar H. H. Wong, Alex Hui, Annelise E. Barron, Naresh Kumar and Mark Willcox
J. Fungi 2025, 11(5), 370; https://doi.org/10.3390/jof11050370 - 12 May 2025
Viewed by 2661
Abstract
With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals [...] Read more.
With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals against Candida albicans, C. tropicalis, C. parapsilosis, Meyerozyma guilliermondii, Nakaseomyces glabratus, Pichia kudriavzevii and Kluyveromyces marxianus, and Candidozyma auris using the checkerboard microdilution test. RK758 was synergistic with fluconazole in 78% of isolates, with the remaining 22% of isolates still showing partial synergy; it showed synergy with amphotericin B in 56% of isolates, and with caspofungin, 78% of isolates exhibited either synergy or partial synergy. TM8 showed synergy with fluconazole in 44% (with partial synergy in another 44%) of isolates, with amphotericin B in 67% of isolates, and with caspofungin in 44% (with partial synergy in another 44%) of isolates. Colistin with fluconazole or caspofungin exhibited synergy or partial synergy in 56% of the isolates. No antagonism was observed in any of the combinations. Additionally, a time-kill assay further demonstrated synergistic activity between fluconazole and TM8 or RK758. The effects of these peptidomimetics on cell membrane integrity were demonstrated in an ergosterol binding assay, supported by SYTOX Green and cellular leakage assays, both indicating a lytic effect. These results suggest that peptidomimetics can synergise with conventional antifungals, offering a potential strategy for combination therapy against yeast infections. The membrane lytic activity of the peptidomimetics likely plays a role in their synergistic interaction with antifungals, thereby enhancing the antimicrobial activities of both compounds at sub-MIC levels. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 4th Edition)
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13 pages, 12905 KB  
Article
Metabolic Influence of S. boulardii and S. cerevisiae in Cross-Kingdom Models of S. mutans and C. albicans
by Ting Li, Xingyi Lu, Yan Wu, Tongtong Wu and Jin Xiao
J. Fungi 2025, 11(4), 325; https://doi.org/10.3390/jof11040325 - 19 Apr 2025
Viewed by 1614
Abstract
Recent studies highlight the potential of Saccharomyces species as probiotics due to their ability to modulate microbial interactions and reduce cariogenic activity, yet the underlying metabolic mechanisms remain unclear. This study investigates the cross-kingdom metabolic effects of Saccharomyces boulardii and Saccharomyces cerevisiae on [...] Read more.
Recent studies highlight the potential of Saccharomyces species as probiotics due to their ability to modulate microbial interactions and reduce cariogenic activity, yet the underlying metabolic mechanisms remain unclear. This study investigates the cross-kingdom metabolic effects of Saccharomyces boulardii and Saccharomyces cerevisiae on the metabolic processes of Streptococcus mutans and Candida albicans using a metabolomics-based approach. Untargeted LC-MS/MS analysis was conducted to assess metabolites in a planktonic model, followed by metabolomic profiling and pathway analysis to identify key metabolic alterations. The results revealed that S. boulardii and S. cerevisiae demonstrated metabolic regulatory effects on S. mutans and C. albicans. Specifically, S. boulardii down-regulated 262 metabolites and up-regulated 168, while S. cerevisiae down-regulated 265 metabolites and up-regulated 168. Both yeast species down-regulated carbohydrate and amino acid metabolism in S. mutans and C. albicans, resulting in reduced biomolecule synthesis and a less acidic environment. S. boulardii and S. cerevisiae also up-regulated certain metabolic processes, including purine metabolism, suggesting a compensatory mechanism for nucleotide synthesis. Notably, dual regulatory effects were observed, where specific metabolites were simultaneously up-regulated and down-regulated, indicating complex metabolic crosstalk. These findings suggest that both S. boulardii and S. cerevisiae modulate microbial metabolism through a shared mechanism, offering potentials for dental caries prevention. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 4th Edition)
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