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New Perspectives for Superficial Fungal Infections

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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 (31 March 2023) | Viewed by 35423

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Special Issue Editors

Prof. Dr. Aditya K. Gupta

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Guest Editor

Division of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada
Interests: onychomycosis; tinea infection; antifungal therapy; antifungal resistance; clinical diagnosis; superficial non-dermatophyte infections
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Bianca Maria Piraccini

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Co-Guest Editor

Dermatology Unit, IRCCS of Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Interests: disorders of skin appendages; skin mycology; fungal nail infections; onychomycosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Technological advances have expanded the clinical perspective of superficial fungi from minor infective species to widespread agents with important roles in the human microbiome. New technologies allow us to better identify fungal agents, leading to an improved understanding of fungal species’ function and detection in infection. Furthermore, greater knowledge of fungal biology promotes a better clinical assessment of superficial fungal infection and enhanced methods of treatment. Thus, new perspectives on these infections are essential to establish optimal therapy routes for future patients.

Aims:

To review the changing biological factors of fungal infection:
- New fungal ID methods/classification;
- Possible changing epidemiology;
- Fungal resistance;
- Biofilms and other new fungal biology.
To address the role of non-dermatophyte fungi in superficial infection;
To provide strategies for improved standard therapies;
To discuss new treatment options/strategies.

Scope:

New classifications of species/epidemiology;
Interaction among dermatophytes/non-dermatophytes/other microbes;
New oral/topical/device therapies;
Immune system impacts of superficial infection;
Improved methods of fungal detection/identification.

Prof. Dr. Aditya K. Gupta
Prof. Dr. Bianca Maria Piraccini
Guest Editors

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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 100 words) can be sent to the Editorial Office for announcement on this website.

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

tinea
Trichophyton
non-dermatophyte
fungal resistance
azoles
terbinafine

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Related Special Issue

New Perspectives for Superficial Fungal Infections, Second Edition in Journal of Fungi (4 articles)

Published Papers (9 papers)

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Research

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12 pages, 3666 KiB

Open AccessArticle

In Vitro and Ex Vivo Biofilm-Forming Ability of Rhinocladiella similis and Trichophyton rubrum Isolated from a Mixed Onychomycosis Case

by Polyana de Souza Costa, Maria Eduarda Basso, Melyssa Negri and Terezinha Inez Estivalet Svidzinski

J. Fungi 2023, 9(7), 696; https://doi.org/10.3390/jof9070696 - 23 Jun 2023

Cited by 2 | Viewed by 1362

Abstract

Infections caused by biofilm-forming agents have important implications for world health. Mixed infections, caused by more than one etiological agent, are also an emerging problem, especially regarding the standardization of effective diagnosis and treatment methods. Cases of mixed onychomycosis (OM) have been reported; however, studies on the microbial interactions between the different fungi in biofilms formed on nails are still scarce. We describe a case of mixed OM caused by the dermatophyte Trichophyton rubrum and the black yeast-like fungus Rhinocladiella similis. Identical growths of both fungi were observed in more than 50 cultures from different nail samples. Additionally, both species were able to form organized single and mixed biofilms, reinforcing the participation of both fungi in the etiology of this OM case. R. similis seemed to grow faster during the process, suggesting that T. rubrum benefits from biofilm development when in combination. Moreover, the biofilm of the Rhinocladiella isolate exhibited exacerbated production of the extracellular matrix, which was not observed with that of a Rhinocladiella reference strain, suggesting that the isolate had natural abilities that were possibly perfected during development in the nail of the patient. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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12 pages, 2043 KiB

Open AccessArticle

Single-Point Nail Sampling to Diagnose Onychomycosis Caused by Non-Dermatophyte Molds: Utility of Polymerase Chain Reaction (PCR) and Histopathology

by Aditya K. Gupta, Elizabeth A. Cooper, Tong Wang, Sara A. Lincoln and Wayne L. Bakotic

J. Fungi 2023, 9(6), 671; https://doi.org/10.3390/jof9060671 - 14 Jun 2023

Cited by 13 | Viewed by 2283

Abstract

The three most commonly used methods for diagnosing non-dermatophyte mold (NDM) onychomycosis are culture, polymerase chain reaction (PCR), and histopathology. Toenail samples from 512 patients (1 sample/patient) with suspected onychomycosis were examined using all three diagnostic tests. A statistically significant association was found between PCR and histopathology results, as well as between fungal culture and histopathology results. All PCR-positive and culture-positive dermatophyte samples were confirmed by histopathology. However, 15/116 (12.9%) of culture-positive NDM samples had negative histopathology results, while all PCR-positive NDM samples were confirmed by histopathology. The overall rate of dermatophyte detection was higher using PCR compared to culture (38.9% vs. 11.7%); the lower rate of NDM detection by PCR (11.7% vs. 38.9%) could be attributed to the restriction of the assay design to seven pre-selected targets. When repeat sampling in the clinic is not possible, a combination of NDM detection by PCR and positive histopathology of hyphae may be a proxy for NDM infection, particularly where the NDM occurs without a concomitant dermatophyte. There was a high degree of correlation between negative PCR and negative histopathology. A negative PCR result with negative histopathology findings may be a reliable proxy for the diagnosis of non-fungal dystrophy. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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16 pages, 5223 KiB

Open AccessArticle

High Diversity of Fusarium Species in Onychomycosis: Clinical Presentations, Molecular Identification, and Antifungal Susceptibility

by Lai-Ying Lu, Jie-Hao Ou, Rosaline Chung-Yee Hui, Ya-Hui Chuang, Yun-Chen Fan and Pei-Lun Sun

J. Fungi 2023, 9(5), 534; https://doi.org/10.3390/jof9050534 - 30 Apr 2023

Cited by 2 | Viewed by 4871

Abstract

Fusarium are uncommon but important pathogenic organisms; they cause non-dermatophyte mould (NDM) onychomycosis. Patients typically respond poorly to treatment owing to Fusarium’s native resistance to multiple antifungal drugs. However, epidemiological data for Fusarium onychomycosis are lacking in Taiwan. We retrospectively reviewed the data of 84 patients with positive Fusarium nail sample cultures at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2020. We aimed to investigate the clinical presentations, microscopic and pathological characteristics, antifungal susceptibility, and species diversity of Fusarium in patients with Fusarium onychomycosis. We enrolled 29 patients using the six-parameter criteria for NDM onychomycosis to determine the clinical significance of Fusarium in these patients. All isolates were subjected to species identification by sequences and molecular phylogeny. A total of 47 Fusarium strains belonging to 13 species in four different Fusarium species complexes (with Fusarium keratoplasticum predominating) were isolated from 29 patients. Six types of histopathology findings were specific to Fusarium onychomycosis, which may be useful for differentiating dermatophytes from NDMs. The results of drug susceptibility testing showed high variation among species complexes, and efinaconazole, lanoconazole, and luliconazole showed excellent in vitro activity for the most part. This study’s primary limitation was its single-centre retrospective design. Our study showed a high diversity of Fusarium species in diseased nails. Fusarium onychomycosis has clinical and pathological features distinct from those of dermatophyte onychomycosis. Thus, careful diagnosis and proper pathogen identification are essential in the management of NDM onychomycosis caused by Fusarium sp. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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17 pages, 2829 KiB

Open AccessArticle

The Antidepressant Sertraline Affects Cell Signaling and Metabolism in Trichophyton rubrum

by Flaviane M. Galvão-Rocha, Carlos H. L. Rocha, Maíra P. Martins, Pablo R. Sanches, Tamires A. Bitencourt, Matthew S. Sachs, Nilce M. Martinez-Rossi and Antonio Rossi

J. Fungi 2023, 9(2), 275; https://doi.org/10.3390/jof9020275 - 20 Feb 2023

Cited by 2 | Viewed by 2984

Abstract

The dermatophyte Trichophyton rubrum is responsible for most human cutaneous infections. Its treatment is complex, mainly because there are only a few structural classes of fungal inhibitors. Therefore, new strategies addressing these problems are essential. The development of new drugs is time-consuming and expensive. The repositioning of drugs already used in medical practice has emerged as an alternative to discovering new drugs. The antidepressant sertraline (SRT) kills several important fungal pathogens. Accordingly, we investigated the inhibitory mechanism of SRT in T. rubrum to broaden the knowledge of its impact on eukaryotic microorganisms and to assess its potential for future use in dermatophytosis treatments. We performed next-generation sequencing (RNA-seq) to identify the genes responding to SRT at the transcript level. We identified that a major effect of SRT was to alter expression for genes involved in maintaining fungal cell wall and plasma membrane stability, including ergosterol biosynthetic genes. SRT also altered the expression of genes encoding enzymes related to fungal energy metabolism, cellular detoxification, and defense against oxidative stress. Our findings provide insights into a specific molecular network interaction that maintains metabolic stability and is perturbed by SRT, showing potential targets for its strategic use in dermatophytosis. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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7 pages, 645 KiB

Open AccessArticle

An Increase in Specialist Treatment for Onychomycosis: An Unexplained Tendency. A Retrospective Study of Patients Treated for Onychomycosis in Danish Hospitals from 1994 to 2018

by Pernille Lindsø Andersen, Isabella Friis Jørgensen, Ditte Marie Lindhardt Saunte, Gregor Borut Jemec, Ole Birger Pedersen and Søren Brunak

J. Fungi 2023, 9(1), 33; https://doi.org/10.3390/jof9010033 - 24 Dec 2022

Cited by 5 | Viewed by 1802

Abstract

Onychomycosis is a common disease with a significant negative impact on quality of life. While the disease is usually manageable in general practice, a proportion of patients need specialist treatment in academic hospital clinics. However, it is an unknown question whether the incidence in those needing specialist treatments is changing. Furthermore, the comorbidity burden in this patient population severely affected by onychomycosis has never been characterized. We conducted a retrospective study on patients treated for onychomycosis in Danish hospitals from 1994 to 2018. The cohort was observed for 24 years, and the data comprise 7.2 million Danes and their hospital diagnoses. A disease trajectory algorithm was used to examine the comorbidity burden in the cohort. A total of 2,271 patients received hospital treatment for onychomycosis during the time period, of which 1358 (59.8%) were men. The data show an increase in the incidence of hospital-treated cases since 2012 and that the most common comorbidities in this patient population include cardiovascular disease, alcohol-related diagnoses, and diabetes. One explanation of the increase in specialist treatment may include a general increase in patients with decreased resilience to fungal disease. This lack of resilience may both include an increasing elderly population with atherosclerosis, diabetes, and immunosuppression but also a potential increase in patients treated with immunosuppressive agents. Another possible explanation may include a shift in patient expectations in the case of treatment failure. Thus, patients may have an increasing demand for specialist treatment. While our data document an increase in the number of patients in need of specialist treatment for onychomycosis, we suggest future research to examine the general incidence of onychomycosis but also whether this increase in an apparently recalcitrant disease may be attributed to increased antifungal resistance, more specialist treatment options, or increased attention to dermatomycoses. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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10 pages, 288 KiB

Open AccessArticle

In Vitro Assessment of Azole and Amphotericin B Susceptibilities of Malassezia spp. Isolated from Healthy and Lesioned Skin

by Wissal Chebil, Najoua Haouas, Elja Eskes, Paul Vandecruys, Sameh Belgacem, Hichem Belhadj Ali, Hamouda Babba and Patrick Van Dijck

J. Fungi 2022, 8(9), 959; https://doi.org/10.3390/jof8090959 - 13 Sep 2022

Cited by 4 | Viewed by 2273

Abstract

Malassezia yeasts have recently gained medical importance as emerging pathogens associated with a wide range of dermatological and systemic infections. Since standardized methods for in vitro antifungal susceptibility testing have not yet been established for Malassezia spp., related diseases are always treated empirically. As a result, a high rate of recurrence and decreased antifungal susceptibility have appeared. Thus, the aims of the study were to assess and analyze the in vitro susceptibility of Malassezia isolated from pityriasis versicolor (PV) lesions and healthy controls. A total of 58 Malassezia strains isolated from PV patients and healthy controls were tested. In vitro antifungal susceptibility testing was conducted using the CLSI broth microdilution with some modifications. Candida spp. criteria established in accordance with CLSI guidelines were used for data interpretation. Ketoconazole and posaconazole seemed to be the most effective molecules against Malassezia species. However, considerable percentages of itraconazole, fluconazole, and amphotericin B ‘‘resistant’’ strains (27.6%, 29.3%, and 43.1%, respectively) were revealed in this study. Malassezia furfur, M. sympodialis, and M. globosa showed different susceptibility profiles to the drugs tested. These results emphasize the importance of accurately identifying and evaluating the antifungal susceptibility of Malassezia species in order to guide a specific and effective treatment regimen. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

13 pages, 2535 KiB

Open AccessArticle

Synergism between the Antidepressant Sertraline and Caspofungin as an Approach to Minimise the Virulence and Resistance in the Dermatophyte Trichophyton rubrum

by Carlos H. Lopes Rocha, Flaviane M. Galvão Rocha, Tamires A. Bitencourt, Maíra P. Martins, Pablo R. Sanches, Antonio Rossi and Nilce M. Martinez-Rossi

J. Fungi 2022, 8(8), 815; https://doi.org/10.3390/jof8080815 - 3 Aug 2022

Cited by 6 | Viewed by 2309

Abstract

Trichophyton rubrum is responsible for several superficial human mycoses. Novel strategies aimed at controlling this pathogen are being investigated. The objective of this study was to evaluate the antifungal activity of the antidepressant sertraline (SRT), either alone or in combination with caspofungin (CASP). We calculated the minimum inhibitory concentrations of SRT and CASP against T. rubrum. Interactions between SRT and CASP were evaluated using a broth microdilution chequerboard. We assessed the differential expression of T. rubrum cultivated in the presence of SRT or combinations of SRT and CASP. We used MTT and violet crystal assays to compare the effect of SRT alone on T. rubrum biofilms with that of the synergistic combination of SRT and CASP. A human nail infection assay was performed. SRT alone, or in combination with CASP, exhibited antifungal activity against T. rubrum. SRT targets genes involved in the biosyntheses of cell wall and ergosterol. Furthermore, the metabolic activity of the T. rubrum biofilm and its biomass were affected by SRT and the combination of SRT and CASP. SRT alone, or in combination, shows potential as an approach to minimise resistance and reduce virulence. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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Review

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31 pages, 4027 KiB

Open AccessReview

Atypical and Unpredictable Superficial Mycosis Presentations: A Narrative Review

by Zoubir Belmokhtar, Samira Djaroud, Derouicha Matmour and Yassine Merad

J. Fungi 2024, 10(4), 295; https://doi.org/10.3390/jof10040295 - 18 Apr 2024

Cited by 1 | Viewed by 2340

Abstract

While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or joint); mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides; and appearing with unexpected color, shape, or distribution. The emergence of such a challenging clinical picture is attributed to the complex interplay of host characteristics (hygiene and aging population), environment (climate change), advances in medical procedures, and agent factors (fungal resistance and species emergence). We aim to provide a better understanding of unusual epidemiological contexts and atypical manifestations of fungal superficial diseases, knowing that there is no pre-established clinical guide for these conditions. Thus, a literature examination was performed to provide a comprehensive analysis on rare and atypical superficial mycosis as well as an update on certain fungal clinical manifestations and their significance. The research and standard data extraction were performed using PubMed, Medline, Scopus, and EMBASE databases, and a total of 222 articles were identified. This review covers published research findings for the past six months. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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13 pages, 342 KiB

Open AccessReview

Onychomycosis: Old and New

by Narges Maskan Bermudez, Giselle Rodríguez-Tamez, Sofia Perez and Antonella Tosti

J. Fungi 2023, 9(5), 559; https://doi.org/10.3390/jof9050559 - 12 May 2023

Cited by 22 | Viewed by 13683

Abstract

Onychomycosis is a common chronic fungal infection of the nail that causes discoloration and/or thickening of the nail plate. Oral agents are generally preferred, except in the case of mild toenail infection limited to the distal nail plate. Terbinafine and itraconazole are the only approved oral therapies, and fluconazole is commonly utilized off-label. Cure rates with these therapies are limited, and resistance to terbinafine is starting to develop worldwide. In this review, we aim to review current oral treatment options for onychomycosis, as well as novel oral drugs that may have promising results in the treatment of onychomycosis. Full article

(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)

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