Fungal Infections: New Challenges and Opportunities

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 May 2023) | Viewed by 9362

Special Issue Editors


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Guest Editor
1. Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal
2. ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
Interests: biofilms; Candida; AMR; fungal infection; polymicrobial biofilms; alternatives to antifungals
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Co-Guest Editor
Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia
Interests: biofilm; Candida; MRSA; virulence; resistance; farnesol; photodynamic inactivation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Invasive and superficial fungal infections result in a noteworthy global rate of morbidity and mortality. It is recognized that the pathogenicity of fungal species is closely related to the general host immunity state. Indeed, this occurs very commonly as a consequence of other health problems, such as cancer, HIV, denture wearing, tobacco smoking, chemo, and corticosteroid therapies. The quick identification and detection of the fungal species involved in infections is crucial to apply an effective treatment. Additionally, in recent decades, antifungal drug resistance has been growing fast. Taking into consideration the increasing number of fungal species and strains with elevated antifungal drug resistance, it is quite important to search for effective alternative therapies to the current antifungal agents (e.g., natural and synthetic compounds, photodynamic therapy).

This SI intents to present new data on fungal infections, fungal biofilms, novel treatments, and innovative and quick methods (e.g., microfluidic devices, molecular techniques) to identify fungal pathogens. Original articles, case studies, and reviews are welcome.

Dr. Célia F. Rodrigues
Dr. Lucia Černáková
Guest Editors

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Published Papers (5 papers)

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Research

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16 pages, 6421 KiB  
Article
New Insights in Phenothiazinium-Mediated Photodynamic Inactivation of Candida Auris
by Abdênego R. Silva, Fernanda V. Cabral, Camila R. Silva, Daniela F. T. Silva, Anderson Z. Freitas, Adriana Fontes and Martha S. Ribeiro
J. Fungi 2023, 9(7), 717; https://doi.org/10.3390/jof9070717 - 30 Jun 2023
Cited by 1 | Viewed by 1115
Abstract
In recent years, Candida auris has emerged as a hazardous hospital-acquired pathogen. Its resistance to antifungal treatments makes it challenging, requiring new approaches to manage it effectively. Herein, we aimed to assess the impact of photodynamic inactivation mediated by methylene blue (MB-PDI) or [...] Read more.
In recent years, Candida auris has emerged as a hazardous hospital-acquired pathogen. Its resistance to antifungal treatments makes it challenging, requiring new approaches to manage it effectively. Herein, we aimed to assess the impact of photodynamic inactivation mediated by methylene blue (MB-PDI) or 1,9-dimethyl MB (DMMB-PDI) combined with a red LED against C. auris. To evaluate the photoinactivation of yeasts, we quantified colony-forming units and monitored ROS production. To gain some insights into the differences between MB and DMMB, we assessed lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨm). After, we verified the effectiveness of DMMB against biofilms by measuring metabolic activity and biomass, and the structures were analyzed through scanning electron microscopy and optical coherence tomography. We also evaluated the cytotoxicity in mammalian cells. DMMB-PDI successfully eradicated C. auris yeasts at 3 μM regardless of the light dose. In contrast, MB (100 μM) killed cells only when exposed to the highest dose of light. DMMB-PDI promoted higher ROS, LPO and ΔΨm levels than those of MB. Furthermore, DMMB-PDI was able to inhibit biofilm formation and destroy mature biofilms, with no observed toxicity in fibroblasts. We conclude that DMMB-PDI holds great potential to combat the global threat posed by C. auris. Full article
(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities)
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12 pages, 1701 KiB  
Article
Essential Role of CgErg6p in Maintaining Oxidative Stress Tolerance and Iron Homeostasis in Candida glabrata
by Daniel Elias, Nora Tóth Hervay, Marek Bujdos and Yvetta Gbelska
J. Fungi 2023, 9(5), 579; https://doi.org/10.3390/jof9050579 - 17 May 2023
Cited by 2 | Viewed by 1602
Abstract
The human pathogenic fungus Candida glabrata is the second leading cause of candidemia, a life-threatening invasive mycosis. Clinical outcomes are complicated by reduced susceptibility of C. glabrata to azoles together with its ability to evolve stable resistance to both azoles and echinocandins following [...] Read more.
The human pathogenic fungus Candida glabrata is the second leading cause of candidemia, a life-threatening invasive mycosis. Clinical outcomes are complicated by reduced susceptibility of C. glabrata to azoles together with its ability to evolve stable resistance to both azoles and echinocandins following drug exposure. Compared to other Candida spp., C. glabrata displays robust oxidative stress resistance. In this study, we investigated the impact of CgERG6 gene deletion on the oxidative stress response in C. glabrata. CgERG6 gene encodes sterol-24-C-methyltransferase, which is involved in the final steps of ergosterol biosynthesis. Our previous results showed that the Cgerg6Δ mutant has a lower ergosterol content in its membranes. Here, we show that the Cgerg6Δ mutant displays increased susceptibility to oxidative stress inducing agents, such as menadione, hydrogen peroxide and diamide, accompanied with increased intracellular ROS production. The Cgerg6Δ mutant is not able to tolerate higher concentrations of iron in the growth media. We observed increased expression of transcription factors, CgYap1p, CgMsn4p and CgYap5p, together with increased expression of catalase encoding the CgCTA1 gene and vacuolar iron transporter CgCCC1 in the Cgerg6Δ mutant cells. However, it seems that the CgERG6 gene deletion does not influence the function of mitochondria. Full article
(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities)
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13 pages, 655 KiB  
Article
Zerumbone Disturbs the Extracellular Matrix of Fluconazole-Resistant Candida albicans Biofilms
by César Augusto Abreu-Pereira, Ana Luiza Gorayb-Pereira, João Vinícius Menezes Noveletto, Cláudia Carolina Jordão and Ana Cláudia Pavarina
J. Fungi 2023, 9(5), 576; https://doi.org/10.3390/jof9050576 - 16 May 2023
Cited by 2 | Viewed by 1252
Abstract
This study assessed the effect of zerumbone (ZER) against fluconazole-resistant (CaR) and -susceptible Candida albicans (CaS) biofilms and verified the influence of ZER on extracellular matrix components. Initially, to determine the treatment conditions, the minimum inhibitory concentration (MIC), the minimum fungicidal concentration (MFC) [...] Read more.
This study assessed the effect of zerumbone (ZER) against fluconazole-resistant (CaR) and -susceptible Candida albicans (CaS) biofilms and verified the influence of ZER on extracellular matrix components. Initially, to determine the treatment conditions, the minimum inhibitory concentration (MIC), the minimum fungicidal concentration (MFC) and the survival curve were evaluated. Biofilms were formed for 48 h and exposed to ZER at concentrations of 128 and 256 µg/mL for 5, 10 and 20 min (n = 12). One group of biofilms did not receive the treatment in order to monitor the effects. The biofilms were evaluated to determine the microbial population (CFU/mL), and the extracellular matrix components (water-soluble polysaccharides (WSP), alkali-soluble polysaccharides (ASPs), proteins and extracellular DNA (eDNA), as well as the biomass (total and insoluble) were quantified. The MIC value of ZER for CaS was 256 μg/mL, and for CaR, it was 64 μg/mL. The survival curve and the MFC value coincided for CaS (256 μg/mL) and CaR (128 μg/mL). ZER reduced the cellular viability by 38.51% for CaS and by 36.99% for CaR. ZER at 256 µg/mL also reduced the total biomass (57%), insoluble biomass (45%), WSP (65%), proteins (18%) and eDNA (78%) of CaS biofilms. In addition, a reduction in insoluble biomass (13%), proteins (18%), WSP (65%), ASP (10%) and eDNA (23%) was also observed in the CaR biofilms. ZER was effective against fluconazole-resistant and -susceptible C. albicans biofilms and disturbed the extracellular matrix. Full article
(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities)
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8 pages, 283 KiB  
Article
Enhancing of Wound Healing in Burn Patients through Candida albicans β-Glucan
by Fateme Abedini, Shahla Roudbar Mohammadi, Mostafa Dahmardehei, Marjan Ajami, Maryam Salimi, Halala Khalandi, Monireh Mohsenzadegan, Farhad Seif, Bahador Nikoueian Shirvan, Sanaz Yaalimadad, Maryam Roudbary and Célia F. Rodrigues
J. Fungi 2022, 8(3), 263; https://doi.org/10.3390/jof8030263 - 4 Mar 2022
Cited by 5 | Viewed by 2468
Abstract
The mortality and disability-adjusted life years (DALYs) of burn patients are decreasing over time. However, finding novel effective treatment approaches using natural agents is highly considered to reduce the burden of burn injuries. One of the recent agents used in wound healing is [...] Read more.
The mortality and disability-adjusted life years (DALYs) of burn patients are decreasing over time. However, finding novel effective treatment approaches using natural agents is highly considered to reduce the burden of burn injuries. One of the recent agents used in wound healing is β-glucan, mainly extracted from fungi cell walls. This study aimed to evaluate the effect of 5% (m/m) of yeast β-glucan ointment on burn wound healing and to assess the impact of β-glucan on cytokines during the treatment. Thirty-three patients with second or third-degree burns were enrolled in this study. Two groups of twenty-three and ten patients used yeast 5% (m/m) β-glucan ointment (study group) and Stratamed ointment (control), respectively, on a daily basis, for a maximum of four weeks. The size of the burn wounds was measured before and at the end of the treatment. Blood samples of 14 and 10 patients in the β-glucan and control groups, respectively, were obtained before and after the treatment, and the enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum concentration of the IL-4, IL-17, and IFN-γ cytokines. The log-binomial model was used to assess the efficacy of the β-glucan ointment on burn wound healing. ANOVA/ANCOVA was employed to assess the effects of β-glucan on the serum concentration of cytokines. After adjusting for potential confounders/covariates, patients receiving β-glucan had better wound healing (RR = 4.34; 95% CI: 0.73 to 25.67; p = 0.11). There was a significant difference in IL-4 secretion between the β-glucan and control groups after adjusting for potential confounders/covariates (MD = 77.27; 95% CI: 44.73 to 109.82; Cohen’s d = 2.21; 95% CI: 1.16 to 3.24; p = 0.0001). The results indicate that 5% (m/m) of β-glucan has efficacy in burn wound healing, and a significant difference was found in the level of IL-4 after receiving β-glucan. Further studies with a two-arm design and long-term use of ointment are needed to confirm the effect of β-glucan on wound healing and cytokine secretion. Full article
(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities)

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16 pages, 699 KiB  
Systematic Review
Trichoderma spp.-Related Pneumonia: A Case Report in Heart–Lung Transplantation Recipient and a Systematic Literature Review
by Carlo Burzio, Eleonora Balzani, Giorgia Montrucchio, Anna Chiara Trompeo, Silvia Corcione and Luca Brazzi
J. Fungi 2023, 9(2), 195; https://doi.org/10.3390/jof9020195 - 2 Feb 2023
Cited by 2 | Viewed by 1557
Abstract
Opportunistic and hospital-acquired infections are common among recipients of solid organ transplantation. New pathogens are increasingly reported in the intensive care unit (ICU) population. We report a case of a patient who developed Trichoderma spp.-related pneumonia (TRP) after heart–lung transplantation. In the absence [...] Read more.
Opportunistic and hospital-acquired infections are common among recipients of solid organ transplantation. New pathogens are increasingly reported in the intensive care unit (ICU) population. We report a case of a patient who developed Trichoderma spp.-related pneumonia (TRP) after heart–lung transplantation. In the absence of antifungal susceptibility testing, TRP was confirmed by histological examination, and empirical therapy with voriconazole and caspofungin was swiftly initiated. Complete resolution of pneumonia was obtained after prolonged combination therapy. Given the lack of guidelines, we conducted a systematic review to elucidate the diagnostic and therapeutic strategies to apply during Trichoderma infection. After deduplication and selection of full texts, we found 42 articles eligible for the systematic review. Pneumonia seems to be the most common clinical manifestation (31.8%). The most used antifungal therapy was amphotericin B, while combination therapy was also reported (27.3%). All the patients were immunocompromised except for one case. Despite the rarity of Trichoderma spp. infection, the increase in invasive fungal infections is of growing importance in ICU, considering their impact on mortality and the emergence of antifungal resistance. In the absence of prospective and multicenter studies, a review can provide useful insight regarding the epidemiology, clinical manifestations, and management of these unexpected challenges. Full article
(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities)
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