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Alternative Therapeutic Approaches of Candida Infections, 3rd Edition
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Alternative Therapeutic Approaches of Candida Infections, 3rd 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: closed (31 August 2024) | Viewed by 6472

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

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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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Published Papers (5 papers)

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Research

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14 pages, 2875 KiB  
Article
In Vivo Efficacy of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in a Neutropenic Mouse Bloodstream Infection Model
by Dávid Balázsi, Zoltán Tóth, Jeffrey B. Locke, Andrew M. Borman, Lajos Forgács, Noémi Balla, Fruzsina Kovács, Renátó Kovács, Chiaki Amano, Tugba Ilay Baran and László Majoros
J. Fungi 2024, 10(9), 617; https://doi.org/10.3390/jof10090617 - 29 Aug 2024
Viewed by 725
Abstract
Objectives: Rezafungin is the first new drug approved to treat candidaemia and invasive candidiasis in more than 10 years. However, data are scant on the in vivo efficacy of rezafungin and the other three approved echinocandins against different Candida auris clades. Methods: This [...] Read more.
Objectives: Rezafungin is the first new drug approved to treat candidaemia and invasive candidiasis in more than 10 years. However, data are scant on the in vivo efficacy of rezafungin and the other three approved echinocandins against different Candida auris clades. Methods: This study involved 10 isolates representing 4 C. auris clades: South Asian (n = 2), East Asian (n = 2), South African (n = 2), and South American (n = 4, including 2 environmental isolates). In the lethality experiment and fungal tissue burden experiment (kidney, heart, and brain), cyclophosphamide-treated BALB/c male mice were intravenously infected (107 and 8 × 106 colony-forming units [CFU]/mouse, respectively). A 20 mg/kg dose of rezafungin was administered on days 1, 3, and 6. Alternatively, beginning 24 h post-infection, mice received 3 mg/kg of caspofungin, 5 mg/kg of micafungin, or 5 mg/kg of anidulafungin once daily for 6 days. Results: Regardless of isolate and clade, all echinocandin regimens improved survival after 21 days (p = 0.0041 to p < 0.0001). All echinocandins frequently produced >3-log mean CFU/g decreases in the fungal kidney and heart burdens, although some of these decreases were not statistically significant. Rezafungin, regardless of clade, produced 3–5 and 2–4 log CFU/g decreases in the kidney and heart burdens, respectively. Echinocandins did not inhibit fungal growth in the brain. Histopathological examination performed on day 7 showed no fungal cells in the heart and kidneys of rezafungin-treated mice and to a lesser extent, caspofungin-treated mice, regardless of the clinical isolate. All echinocandin-treated mice showed medium and/or large foci of fungal cells in their cerebrum or cerebellum. Conclusions: Regardless of the C. auris clade, rezafungin activity in vivo was comparable to or improved over that of the three previously approved echinocandins. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 3rd Edition)
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15 pages, 1620 KiB  
Article
Potential Activity of Micafungin and Amphotericin B Co-Encapsulated in Nanoemulsion against Systemic Candida auris Infection in a Mice Model
by Gabriel Davi Marena, Gabriela Corrêa Carvalho, Alba Ruiz-Gaitán, Giovana Scaramal Onisto, Beatriz Chiari Manzini Bugalho, Letícia Maria Valente Genezini, Maíra Oliveira Dos Santos, Ana Lígia Blanco, Marlus Chorilli and Tais Maria Bauab
J. Fungi 2024, 10(4), 253; https://doi.org/10.3390/jof10040253 - 27 Mar 2024
Viewed by 1369
Abstract
The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations [...] Read more.
The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by C. auris. NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij® 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with Candida auris CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by C. auris can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 3rd Edition)
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14 pages, 2974 KiB  
Article
Therapeutic Use of the Antimicrobial Peptide PNR20 to Resolve Disseminated Candidiasis in a Murine Model
by Jeisson Micelly-Moreno, Adriana Barreto-Santamaría, Gabriela Arévalo-Pinzón, Carolina Firacative, Beatriz L. Gómez, Patricia Escandón, Manuel A. Patarroyo and Julián E. Muñoz
J. Fungi 2023, 9(12), 1149; https://doi.org/10.3390/jof9121149 - 28 Nov 2023
Viewed by 1458
Abstract
Invasive fungal infections (IFIs) caused by Candida species are an emerging threat globally, given that patients at-risk and antifungal resistance are increasing. Antimicrobial peptides (AMPs) have shown good therapeutic capacity against different multidrug-resistant (MDR) microorganisms. This study evaluated the activity of the synthetic [...] Read more.
Invasive fungal infections (IFIs) caused by Candida species are an emerging threat globally, given that patients at-risk and antifungal resistance are increasing. Antimicrobial peptides (AMPs) have shown good therapeutic capacity against different multidrug-resistant (MDR) microorganisms. This study evaluated the activity of the synthetic peptide, PNR20, against Candida albicans ATCC 10231 and a MDR Colombian clinical isolate of Candida auris. Perturbation of yeast cell surface was evaluated using scanning electron microscopy. Cell viability of Vero cells was determined to assess peptide toxicity. Additionally, survival, fungal burden, and histopathology of BALB/c mice infected intravenously with each Candida species and treated with PNR20 were analyzed. Morphological alterations were identified in both species, demonstrating the antifungal effect of PNR20. In vitro, Vero cells’ viability was not affected by PNR20. All mice infected with either C. albicans or C. auris and treated with PNR20 survived and had a significant reduction in the fungal burden in the kidney compared to the control group. The histopathological analysis in mice infected and treated with PNR20 showed more preserved tissues, without the presence of yeast, compared to the control groups. This work shows that the utilization of PNR20 is a promising therapeutic alternative against disseminated candidiasis. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 3rd Edition)
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Review

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23 pages, 1427 KiB  
Review
Azole Combinations and Multi-Targeting Drugs That Synergistically Inhibit Candidozyma auris
by Stephanie Toepfer, Mikhail V. Keniya, Michaela Lackner and Brian C. Monk
J. Fungi 2024, 10(10), 698; https://doi.org/10.3390/jof10100698 - 7 Oct 2024
Viewed by 580
Abstract
Limited antifungal treatment options and drug resistance require innovative approaches to effectively combat fungal infections. Combination therapy is a promising strategy that addresses these pressing issues by concurrently targeting multiple cellular sites. The drug targets usually selected for combination therapy are from different [...] Read more.
Limited antifungal treatment options and drug resistance require innovative approaches to effectively combat fungal infections. Combination therapy is a promising strategy that addresses these pressing issues by concurrently targeting multiple cellular sites. The drug targets usually selected for combination therapy are from different cellular pathways with the goals of increasing treatment options and reducing development of resistance. However, some circumstances can prevent the implementation of combination therapy in clinical practice. These could include the increased risk of adverse effects, drug interactions, and even the promotion of drug resistance. Furthermore, robust clinical evidence supporting the superiority of combination therapy over monotherapy is limited and underscores the need for further research. Despite these challenges, synergies detected with different antifungal classes, such as the azoles and echinocandins, suggest that treatment strategies can be optimized by better understanding the underlying mechanisms. This review provides an overview of multi-targeting combination strategies with a primary focus on Candidozyma auris infections. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 3rd Edition)
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23 pages, 1730 KiB  
Review
Current Perspectives of Antifungal Therapy: A Special Focus on Candida auris
by Arumugam Ganeshkumar, Manickam Muthuselvam, Patricia Michelle Nagai de Lima, Rajendren Rajaram and Juliana Campos Junqueira
J. Fungi 2024, 10(6), 408; https://doi.org/10.3390/jof10060408 - 6 Jun 2024
Viewed by 1648
Abstract
Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and [...] Read more.
Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 3rd Edition)
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