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Fungal Infections: New Challenges and Opportunities, 2nd Edition

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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 (30 September 2024) | Viewed by 20448

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Dr. Célia F. Rodrigues

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1. 1H-TOXRUN—One Health Toxicology Research Unit, CESPU-IUCS, Gandra, Portugal
2. LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, University of Porto, 4200-465 Porto, Portugal
Interests: biofilms; candida resistance; fungal and bacterial infections; resistance to antimicrobials; pathogens detection; alternative therapies
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Dr. Lucia Černáková

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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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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

fungi
infection
antifungal resistance
Candida spp.
Aspergillus spp.
co-infection
detection method
identification
alternative treatment
virulence

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Related Special Issue

Fungal Infections: New Challenges and Opportunities, 3rd Edition in Journal of Fungi (5 articles)

Published Papers (10 papers)

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Research

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17 pages, 320 KiB

Open AccessArticle

The Role of Rotational Thromboelastometry in Early Detection of the Hemostatic Derangements in Neonates with Systemic Candida Infection

by Rozeta Sokou, Alexia Eleftheria Palioura, Aikaterini Konstantinidi, Alexandra Lianou, Maria Lampridou, Martha Theodoraki, Daniele Piovani, Stefanos Bonovas, Konstantina A. Tsante, Petros Ioannou, Nicoletta Iacovidou and Andreas G. Tsantes

J. Fungi 2025, 11(1), 17; https://doi.org/10.3390/jof11010017 - 30 Dec 2024

Cited by 1 | Viewed by 938

Abstract

Background: Systemic Candida infection (SCI) is the third most common cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). While platelet involvement in fungal infections has been extensively studied, evaluation of the hemostatic mechanism in Candida infections, especially in neonates, has not been widely investigated. The aim of the current study was to evaluate the hemostatic profile of neonates with SCI through rotational thromboelastometry (ROTEM), a laboratory method that assesses the viscoelastic properties of blood. Methods: This is a single-centered prospective cohort study including a group of neonates with SCI (n = 21); the control group consisted of healthy neonates (n = 24). Demographics, clinical parameters, and laboratory data were recorded at the disease onset. Neonatal scores for the assessment of disease severity (Modified NEOMOD, nSOFA, and NeoBAT) were also calculated. ROTEM parameters of neonates with SCI were compared to those of healthy neonates. Results: ROTEM parameters differed between neonates with SCI and healthy neonates, indicating a hypocoagulable profile of infected neonates. Specifically, neonates with SCI had significantly prolonged clotting time (CT) and clot formation time (CFT), as well as lower clot amplitude at 10 min (A10) and maximum clot firmness (MCF) when compared to healthy neonates (p values < 0.05), findings that remained consistent after adjusting for confounding factors such as gestational age, birth weight, and sex. In addition, a strong correlation was noted between ROTEM parameters and disease severity based on the modified NEOMOD, nSOFA, and NeoBAT scores. Conclusions: ROTEM parameters revealed a hypocoagulable profile in neonates during the early stages of SCI, which is also associated with disease severity. The results of this study highlight the need for monitoring of hemostatic status of this vulnerable group of patients and indicate that ROTEM analysis may have a role in the early detection of the hemostatic derangements associated with SCI in neonates, in order to ensure timely diagnosis and targeted therapeutic intervention. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

21 pages, 4681 KiB

Open AccessArticle

Evaluation of Fifteen 5,6-Dihydrotetrazolo[1,5-c]quinazolines Against Nakaseomyces glabrata: Integrating In Vitro Studies, Molecular Docking, QSAR, and In Silico Toxicity Assessments

by Lyudmyla Antypenko, Oleksii Antypenko, Alina Fominichenko, Iryna Karnaukh, Serhii Kovalenko and Mieko Arisawa

J. Fungi 2024, 10(12), 816; https://doi.org/10.3390/jof10120816 - 25 Nov 2024

Cited by 1 | Viewed by 1046

Abstract

Nakaseomyces glabrata (Candida glabrata), the second most prevalent Candida pathogen globally, has emerged as a major clinical threat due to its ability to develop high-level azole resistance. In this study, two new 5,6-dihydrotetrazolo[1,5-c]quinazoline derivatives (c11 and c12) were synthesized and characterized using IR, LC-MS, ¹H, and ¹³C NMR spectra. Along with 13 previously reported analogues, these compounds underwent in vitro antifungal testing against clinical N. glabrata isolates using a serial dilution method (0.125–64 mg/L). Remarkably, compounds c5 and c1 exhibited potent antifungal activity, with minimum inhibitory concentrations of 0.37 μM and 0.47 μM, respectively—about a 20-fold improvement in μM concentration over standard drugs like amphotericin B, caspofungin, and micafungin. A detailed structure–activity relationship analysis revealed crucial molecular features enhancing antifungal potency. Extensive molecular docking studies across 18 protein targets explored potential binding pockets and affinities of the lead compounds. A robust 3D-QSAR model, incorporating molecular descriptors Mor26m and Mor29e, displayed good predictive ability for antifungal activity. In silico predictions indicated an absence of herbicidal effect, negligible environmental toxicity (to honeybees, avian species, and aquatic organisms), and mild human toxicity concerns for these compounds. This comprehensive approach aims to develop novel and effective antifungal compounds against the clinically relevant pathogen N. glabrata. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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14 pages, 322 KiB

Open AccessArticle

Prevalence and Risk Factors Predicting Onychomycosis in Patients with and Without Diabetes Mellitus in Spain: A Cross-Sectional Study

by David Navarro-Pérez, José Luis Lázaro-Martínez, Sara García-Oreja, Teresa Pérez-Pérez, Francisco Javier Álvaro-Afonso and Aroa Tardáguila-García

J. Fungi 2024, 10(11), 790; https://doi.org/10.3390/jof10110790 - 14 Nov 2024

Cited by 2 | Viewed by 1721

Abstract

Background: A cross-sectional study was conducted to investigate the prevalence of onychomycosis (ONM) and its causative pathogens in populations with and without diabetes in Spain. The association between the presence of ONM, different risk factors, and comorbidities was also examined. Methodology: A total of 160 patients with diabetes and 160 individuals without diabetes were recruited consecutively. A single investigator recorded the relative data of each patient and sampled nail dust and detritus for microbiological culture and polymerase chain reaction (PCR) analyses of patients who showed clinical signs of fungal infection. Results: The prevalence of ONM was 36.88% (59/160) in the population with diabetes, 17.5% (28/160) in the population without diabetes, and 34.35% (45/131) in the population with diabetic foot. Dermatophyte fungi were most frequently identified, although the proportion was higher among those without diabetes than those with diabetes (19/28 and 28/59, respectively). However, the rate of mixed infections was higher in the population with diabetes compared to those without diabetes (13/59 and 2/28, respectively). A statistically significant association was found between the presence of diabetes and the risk of ONM (p < 0.001; odds ratio (OR) = 2.754; 95% confidence interval (CI) 1.652–4.679). The risk factors associated with ONM among the patients with diabetes were a history of minor amputation, revascularisation, or cardiovascular disease, a low educational level, HbA1c values > 7%, hyperkeratosis, and subungual detritus. Among the patients without diabetes, nail thickening and chromonychia were associated with ONM. Conclusion: The results of this study suggest that the early diagnosis of ONM and knowledge of risk factors among patients with diabetes could enable the prevention of ONM, complications, and serious injuries through education for professionals and patients. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

12 pages, 1106 KiB

Open AccessArticle

Predicting Fungemia in the ICU: Unveiling the Value of Weekly Fungal Surveillance and Yeast Colonisation Monitoring

by Pedro Suárez-Urquiza, Javier Pemán, Monica Gordon, Patricio Favier, Paula Muñoz-Brell, Jose Luis López-Hontangas and Alba Ruiz-Gaitán

J. Fungi 2024, 10(10), 674; https://doi.org/10.3390/jof10100674 - 27 Sep 2024

Cited by 1 | Viewed by 1446

Abstract

Fungemia remains a major threat in intensive care units (ICUs), with high mortality rates despite advances in diagnostics and treatment. Colonisation by yeasts is an independent risk factor for fungemia; however, its predictive utility requires further research. In this 8-year study, we analysed 38,017 samples from 3206 patients and 171 fungemia episodes as part of a weekly fungal surveillance programme. We evaluated species-specific colonisation patterns, the predictive value of the Colonisation Index (CI) and Corrected Colonisation Index (CCI), and candidemia risks associated with different yeast species and anatomical site colonisation. Our results showed that C. auris, N. glabratus, and C. parapsilosis colonisation increased with longer hospital stays (0.8% to 11.55%, 8.13% to 16.8%, and 1.93% to 5.14%, respectively). The CI and CCI had low discriminatory power (AUROC 67% and 66%). Colonisation by any yeast genera demonstrated high sensitivity (98.32%) and negative predictive value (NPV) (95.90%) but low specificity and positive predictive value (PPV) (23.90% and 6.64%). Tracheal and urine cultures had the highest PPV (15.64% and 12.91%), while inguinal cultures had the highest NPV (98.60%). C. auris (12.32%) and C. parapsilosis (5.5%) were associated with a higher fungemia risk (log-rank < 0.001). These findings support the use of weekly surveillance to better stratify the fungemia risk and optimise antifungal use in ICUs. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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13 pages, 1122 KiB

Open AccessArticle

Development of a Multiplex Real-Time PCR Assay for the Simultaneous Detection of Two Fungal Pathogens Causing Pneumonia

by Ho-Jae Lim, Seojin Ahn, Jee-Hyun No, Min-Young Park, Min-Jin Kim, Yong-Hak Sohn, Kwang-Soo Shin, Jung-Eun Park and Yong-Jin Yang

J. Fungi 2024, 10(9), 619; https://doi.org/10.3390/jof10090619 - 29 Aug 2024

Viewed by 1583

Abstract

Infectious diseases caused by fungal sources are of great interest owing to their increasing prevalence. Invasive fungal infections, including invasive pulmonary aspergillosis caused by Aspergillus fumigatus, and Pneumocystis pneumonia caused by Pneumocystis jirovecii, are significant causes of morbidity and mortality among immunocompromised patients. The accurate and timely detection of these pathogens in this high-risk population is crucial for effective patient management. We developed a multiplex real-time polymerase chain reaction (PCR) assay, RF2 mRT-PCR, specifically designed to detect two respiratory fungi, P. jirovecii and A. fumigatus, and evaluated its performance in specimens of patients with lower respiratory tract infection. The performance was evaluated using 731 clinical samples, 55 reference species, and one synthetic DNA. The reproducibility test yielded a probit curve with a lower limit of detection of 19.82 copies/reaction for P. jirovecii and 64.20 copies/reaction for A. fumigatus. The RF2 mRT-PCR assay did not cross-react with non-A. fumigatus Aspergillus species or other common bacterial and viral species, and showed 100% in vitro sensitivity and specificity with reference assays. Additionally, it simultaneously detected A. fumigatus and P. jirovecii in co-infected samples. Therefore, the RF2 mRT-PCR assay is an efficient and reliable tool for in vitro diagnosis of A. fumigatus and P. jirovecii pulmonary infections. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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18 pages, 3616 KiB

Open AccessArticle

Candida tropicalis Affects Candida albicans Virulence by Limiting Its Capacity to Adhere to the Host Intestinal Surface, Leading to Decreased Susceptibility to Colitis in Mice

by Kyle Roberts, Abdullah Osme, Carlo De Salvo, Eleonora Zoli, Janet Herrada, Thomas S. McCormick, Mahmoud Ghannoum, Fabio Cominelli and Luca Di Martino

J. Fungi 2024, 10(4), 245; https://doi.org/10.3390/jof10040245 - 25 Mar 2024

Cited by 3 | Viewed by 2186

Abstract

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity of the fungus to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of a C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. The colitis severity was evaluated using histology and a colonoscopy. The mice were mono-inoculated with C. albicans or C. tropicalis or co-challenged with both species. The mice were administered 3% DSS to induce acute colitis. The biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) and dry-weight assays. The abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. The co-challenged mice showed a decreased colitis severity compared to the mono-inoculated mice. The dry-weight assay demonstrated a marked decrease in C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface, leading to a reduction in biofilm formation. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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12 pages, 694 KiB

Open AccessArticle

Frequency of Detection of Candida auris Colonization Outside a Highly Endemic Setting: What Is the Optimal Strategy for Screening of Carriage?

by Laura Magnasco, Malgorzata Mikulska, Chiara Sepulcri, Nadir Ullah, Daniele Roberto Giacobbe, Antonio Vena, Vincenzo Di Pilato, Edward Willison, Andrea Orsi, Giancarlo Icardi, Anna Marchese and Matteo Bassetti

J. Fungi 2024, 10(1), 26; https://doi.org/10.3390/jof10010026 - 29 Dec 2023

Cited by 8 | Viewed by 2228

Abstract

Candida auris outbreaks are increasingly frequent worldwide. In our 1000-bed hospital, an endemic transmission of C. auris was established in two of five intensive care units (ICUs). Aims of our study were to describe the occurrence of new cases of C. auris colonization and infection outside the endemic ICUs, in order to add evidence for future policies on screening in patients discharged as negative from an endemic setting, as well as to propose a new algorithm for screening of such high-risk patients. From 26 March 2021 to 26 January 2023, among 392 patients who were diagnosed as colonized or infected with C. auris in our hospital, 84 (21.4%) received the first diagnosis of colonization or infection outside the endemic ICUs. A total of 68 patients out of 84 (81.0%) had a history of prior admission to the endemic ICUs. All were screened and tested negative during their ICU stay with a median time from last screening to discharge of 3 days. In 57/68 (83.8%) of patients, C. auris was detected through screening performed after ICU discharge, and 90% had C. auris colonization detected within 9 days from ICU discharge. In 13 cases (13/57 screened, 22.8%), the first post-ICU discharge screening was negative. In those not screened, candidemia was the most frequent event of the first C. auris detection (6/11 patients not screened). In settings where the transmission of C. auris is limited to certain wards, we suggest screening both at discharge from the endemic ward(s) even in case of a recent negative result, and at least twice after admission to nonendemic settings. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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Review

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16 pages, 733 KiB

Open AccessReview

Fungal Infections in the Caribbean: A Review of the Literature to Date

by Nicole Gousy, Bharadwaj Adithya Sateesh, David W. Denning, Krystal Latchman, Edmond Mansoor, Jillwin Joseph and Prasanna Honnavar

J. Fungi 2023, 9(12), 1177; https://doi.org/10.3390/jof9121177 - 8 Dec 2023

Cited by 1 | Viewed by 2795

Abstract

The most common fungal infections reported from the Caribbean include dermatophytosis, candidiasis, pneumocystis, aspergillosis, histoplasmosis, and cryptococcosis. The Caribbean is hyperendemic for histoplasmosis, with high population exposures. Fungal infections are a significant public health problem in the Caribbean, with rates varying depending on the specific country or region. In Trinidad and Tobago, the fungal burden accounts for 3.3% of the 1.4 million population, while in Jamaica, with a population of 2.9 million, over 57,600 people suffer from fungal infections each year. A study in the Dominican Republic estimated that approximately 221,027 (2%) of over 10 million people have a serious fungal infection. Fungal infections accounts for 21.9% of all skin infections in Haiti. The diagnosis of fungal infections in the Caribbean can be challenging, as access to laboratory testing and specialized medical services is limited in many areas. Access to antifungal medications can also be a challenge in some areas, and antifungal resistance has been reported. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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Other

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10 pages, 1312 KiB

Open AccessCase Report

Navigating Uncertainty: Managing Influenza-Associated Invasive Pulmonary Aspergillosis in an Intensive Care Unit

by Giacomo Casalini, Andrea Giacomelli, Laura Galimberti, Riccardo Colombo, Laura Milazzo, Dario Cattaneo, Antonio Castelli and Spinello Antinori

J. Fungi 2024, 10(9), 639; https://doi.org/10.3390/jof10090639 - 7 Sep 2024

Viewed by 1648

Abstract

We present a challenging case of a patient admitted to an intensive care unit with influenza-associated pulmonary aspergillosis (IAPA). The clinical course was characterised by refractory fungal pneumonia and tracheobronchitis, suspected drug-induced liver injury due to triazole antifungals, and secondary bacterial infections with multidrug-resistant microorganisms, resulting in a fatal outcome despite the optimisation of antifungal treatment through therapeutic drug monitoring. This case underscores the complexity that clinicians face in managing critically ill patients with invasive fungal infections. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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20 pages, 1526 KiB

Open AccessSystematic Review

Are Mouthwashes Really Effective against Candida spp.?

by Marie Maziere, Paulo Rompante, José Carlos Andrade and Célia F. Rodrigues

J. Fungi 2024, 10(8), 528; https://doi.org/10.3390/jof10080528 - 29 Jul 2024

Cited by 2 | Viewed by 3335

Abstract

Oral candidiasis is an opportunistic infection caused by fungi of the genus Candida. Nystatin, fluconazole, and miconazole are the most widely used antifungal drugs in dentistry, but in recent years, they have been shown to be less effective due to the increase in the resistance to antifungal drugs. The growing challenge of antifungal resistance emphasizes the importance of exploring not only alternative strategies in the fight against Candida spp. infections but also supportive treatment for pharmacological treatment for oral candidiasis. This review aims to evaluate and compare the in vitro reports on antifungal efficacy against Candida spp. exhibited by mouthwashes distributed on the European market. The research question was elaborated through the PEO framework recommended by PRISMA 2020. A bibliographic search strategy was developed for the scientific online databases Pubmed and ScienceDirect. According to the eligibility criteria, 21 papers were included in this study over a 27-year period. Mouthwashes containing chlorhexidine digluconate, cetylpyridinium chloride, hexetidine, and fluorine compounds among others, and natural antimicrobials, such as menthol, thymol, eucalyptol, and Glycyrrhiza glabra extracts, have demonstrated antifungal effectiveness. Nonetheless, the methodological variance introduces ambiguity concerning the comparative efficacy of distinct molecules or mouthwash formulations and complicates the evaluation and the comparison of results between studies. Some mouthwashes commercially available in Europe have the potential to be used in anti-Candida therapy and prevention since they have shown antifungal effect. Full article

(This article belongs to the Special Issue Fungal Infections: New Challenges and Opportunities, 2nd Edition)

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