Dermatophytes and Dermatophytoses

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 January 2023) | Viewed by 22878

Special Issue Editors


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Guest Editor
Laboratory for Medical Microbiology, Mölbis, Germany
Interests: medical fungi; dermatophytes; modern diagnostic methods; treatment in dermatomycology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
Interests: medical fungi; dermatomycosis; sexually transmitted infections; skin microbiome, diagnostic methods
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dermatomycosis caused by dermatophytes is one of the most common superficial infections, and if one takes onychomycosis or tinea unguium into account, dermatophyte infections most likely outnumber bacterial skin infections. Infections caused by the genus Trichophyton have the highest clinical significance among those caused by the seven genera known today as per the new taxonomy of dermatophytes. Trichophyton rubrum, the most common anthropophilic dermatophyte worldwide, is currently being increasingly replaced by other species, with Trichophyton interdigitale being one such species. However, the epidemic-like spread of the molecular offshoot Trichophyton mentagrophytes, the internal transcribed spacer (ITS) genotype VIII on the Indian subcontinent, and now having increasingly been reported in several countries across the globe, is causing increasing concern. Trichophyton mentagrophytes ITS VIII has currently been classified as the new species of Trichophyton indotineae. Irrespective of the two names used interchangeably, they are molecularly identical and demonstrate terbinafine resistance in vitro and relevant point mutations in the squalene epoxidase gene. The other dermatophyte regarded as an emerging pathogen is Trichophyton tonsurans as a causative agent of not only tinea gladiatorum, but also of the so-called barbershop mycosis (Tinea capitis et faciei due to Trichophyton tonsurans). Additionally, zoophilic dermatophyte species such as Trichophyton quinckeanum and Trichophyton benhamiae are causing concern, with the latter dermatophyte spreading almost explosively in times of the SARS-CoV-2 pandemic, especially in Germany.

We endeavor to dedicate this Special Issue to significant infections caused by the genus Trichophyton, in the hopes that it will be an easily accessible resource under one umbrella.

Prof. Dr. Pietro Nenoff
Dr. Philipp P. Bosshard
Guest Editors

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Keywords

  • recalcitrant tinea
  • Trichophyton mentagrophytes ITS genotype VIII and Trichophyton indotineae
  • misuse of topical steroids (clobetasol) (an undeniable link, experiences from the Indian subcontinent)
  • terbinafine resistance
  • squalene epoxidase gene
  • itraconazole
  • zoophilic dermatophytes

Published Papers (8 papers)

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Research

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9 pages, 1594 KiB  
Communication
Survey on Dermatophytes Isolated from Animals in Switzerland in the Context of the Prevention of Zoonotic Dermatophytosis
by Marina Fratti, Olympia Bontems, Karine Salamin, Emmanuella Guenova and Michel Monod
J. Fungi 2023, 9(2), 253; https://doi.org/10.3390/jof9020253 - 14 Feb 2023
Cited by 2 | Viewed by 1699
Abstract
Most inflammatory dermatophytoses in humans are caused by zoophilic and geophilic dermatophytes. Knowledge of the epidemiology of these fungi in animals facilitates the prevention of dermatophytosis of animal origin in humans. We studied the prevalence of dermatophyte species in domestic animals in Switzerland [...] Read more.
Most inflammatory dermatophytoses in humans are caused by zoophilic and geophilic dermatophytes. Knowledge of the epidemiology of these fungi in animals facilitates the prevention of dermatophytosis of animal origin in humans. We studied the prevalence of dermatophyte species in domestic animals in Switzerland and examined the effectiveness of direct mycological examination (DME) for their detection compared to mycological cultures. In total, 3515 hair and skin samples, collected between 2008 and 2022 by practicing veterinarians, were subjected to direct fluorescence microscopy and fungal culture. Overall, 611 dermatophytes were isolated, of which 547 (89.5%) were from DME-positive samples. Cats and dogs were the main reservoirs of Trichophyton mentagrophytes and Microsporum canis, whereas Trichophyton benhamiae was predominantly found in guinea pigs. Cultures with M. canis significantly (p < 0.001) outnumbered those with T. mentagrophytes in DME-negative samples (19.3% versus 6.8%), possibly because M. canis can be asymptomatic in cats and dogs, unlike T. mentagrophytes, which is always infectious. Our data confirm DME as a reliable, quick, and easy method to identify the presence of dermatophytes in animals. A positive DME in an animal hair or skin sample should alert people in contact with the animal to the risk of contracting dermatophytosis. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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13 pages, 1572 KiB  
Article
Antifungal and Antibiofilm Activity of Riparin III against Dermatophytes
by Emanuel Pereira Silva, Marcelo Antônio Nóbrega da Rocha, Risley Nikael Medeiros Silva, Juliana Moura-Mendes, Gabriela Ribeiro de Sousa, Jailton de Souza-Ferrari, José Maria Barbosa-Filho, Edeltrudes de Oliveira Lima and Fillipe de Oliveira Pereira
J. Fungi 2023, 9(2), 231; https://doi.org/10.3390/jof9020231 - 09 Feb 2023
Cited by 2 | Viewed by 1456
Abstract
The ability of dermatophytes to develop biofilms is possibly involved in therapeutic failure because biofilms impair drug effectiveness in the infected tissues. Research to find new drugs with antibiofilm activity against dermatophytes is crucial. In this way, riparins, a class of alkaloids that [...] Read more.
The ability of dermatophytes to develop biofilms is possibly involved in therapeutic failure because biofilms impair drug effectiveness in the infected tissues. Research to find new drugs with antibiofilm activity against dermatophytes is crucial. In this way, riparins, a class of alkaloids that contain an amide group, are promising antifungal compounds. In this study, we evaluated the antifungal and antibiofilm activity of riparin III (RIP3) against Trichophyton rubrum, Microsporum canis, and Nannizzia gypsea strains. We used ciclopirox (CPX) as a positive control. The effects of RIP3 on fungal growth were evaluated by the microdilution technique. The quantification of the biofilm biomass in vitro was assessed by crystal violet, and the biofilm viability was assessed by quantifying the CFU number. The ex vivo model was performed on human nail fragments, which were evaluated by visualization under light microscopy and by quantifying the CFU number (viability). Finally, we evaluated whether RIP3 inhibits sulfite production in T. rubrum. RIP3 inhibited the growth of T. rubrum and M. canis from 128 mg/L and N. gypsea from 256 mg/L. The results showed that RIP3 is a fungicide. Regarding antibiofilm activity, RIP3 inhibited biofilm formation and viability in vitro and ex vivo. Moreover, RIP3 inhibited the secretion of sulfite significantly and was more potent than CPX. In conclusion, the results indicate that RIP3 is a promising antifungal agent against biofilms of dermatophytes and might inhibit sulfite secretion, one relevant virulence factor. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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13 pages, 2105 KiB  
Article
Metagenomics of Toenail Onychomycosis in Three Victorian Regions of Australia
by Steven Hainsworth, Ann C. Lawrie, Thiru Vanniasinkam and Danilla Grando
J. Fungi 2022, 8(11), 1198; https://doi.org/10.3390/jof8111198 - 14 Nov 2022
Cited by 1 | Viewed by 2322
Abstract
Onychomycosis is a fungal disease of the nail that is found worldwide and is difficult to diagnose accurately. This study used metagenomics to investigate the microbiology of 18 clinically diagnosed mycotic nails and two normal nails for fungi and bacteria using the ITS2 [...] Read more.
Onychomycosis is a fungal disease of the nail that is found worldwide and is difficult to diagnose accurately. This study used metagenomics to investigate the microbiology of 18 clinically diagnosed mycotic nails and two normal nails for fungi and bacteria using the ITS2 and 16S loci. Four mycotic nails were from Bass Coast, six from Melbourne Metropolitan and eight from Shepparton, Victoria, Australia. The mycotic nails were photographed and metagenomically analysed. The ITS2 sequences for T. rubrum and T. interdigitale/mentagrophytes averaged over 90% of hits in 14/18 nails. The high abundance of sequences of a single dermatophyte, compared to all other fungi in a single nail, made it the most likely infecting agents (MLIA). Trichophyton rubrum and T. interdigitale/mentagrophytes were found in Bass Coast and Shepparton while only T. interdigitale/mentagrophytes was found in Melbourne. Two nails with T. interdigitale/mentagrophytes mixed with high abundance non-dermatophyte moulds (NDMs) (Aspergillus versicolor, Acremonium sclerotigenum) were also observed. The two control nails contained chiefly Fusarium oxysporum and Malassezia slooffiae. For bacteria, Staphylococcus epidermidis was in every nail and was the most abundant, including the control nails, with an overall mean rate of 66.01%. Rothia koreensis, Corynebacterium tuberculostearicum, and Brevibacterium sediminis also featured. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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12 pages, 1770 KiB  
Article
MALDI-TOF Mass Spectrometry Online Identification of Trichophyton indotineae Using the MSI-2 Application
by Anne-Cécile Normand, Alicia Moreno-Sabater, Arnaud Jabet, Samia Hamane, Geneviève Cremer, Françoise Foulet, Marion Blaize, Sarah Dellière, Christine Bonnal, Sébastien Imbert, Sophie Brun, Ann Packeu, Stéphane Bretagne and Renaud Piarroux
J. Fungi 2022, 8(10), 1103; https://doi.org/10.3390/jof8101103 - 19 Oct 2022
Cited by 12 | Viewed by 2045
Abstract
Trichophyton indotineae is an emerging pathogen which recently spread from India to Europe and that is more prone than other species of the Trichophyton mentagrophytes complex to show resistance to terbinafine, resulting in the necessity of rapid identification. Here, we improved the online [...] Read more.
Trichophyton indotineae is an emerging pathogen which recently spread from India to Europe and that is more prone than other species of the Trichophyton mentagrophytes complex to show resistance to terbinafine, resulting in the necessity of rapid identification. Here, we improved the online MSI-2 MALDI-TOF identification tool in order to identify T. indotineae. By multiplying the culture conditions (2 culture media and 6 stages of growth) prior to protein extractions for both test isolates and reference strains, we added 142 references corresponding to 12 strains inside the T. mentagrophytes complex in the online MSI-2 database, of which 3 are T. indotineae strains. The resulting database was tested with 1566 spectra of 67 isolates from the T. mentagrophytes complex, including 16 T. indotineae isolates. Using the newly improved MSI-2 database, we increased the identification rate of T. indotineae from 5% to 96%, with a sensitivity of 99.6%. We also identified specific peaks (6834/6845 daltons and 10,634/10,680 daltons) allowing for the distinction of T. indotineae from the other species of the complex. Our improved version of the MSI-2 application allows for the identification of T. indotineae. This will improve the epidemiological knowledge of the spread of this species throughout the world and will help to improve patient care. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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11 pages, 751 KiB  
Article
Identification of Dermatophyte and Non-Dermatophyte Agents in Onychomycosis by PCR and DNA Sequencing—A Retrospective Comparison of Diagnostic Tools
by Isabella Pospischil, Charlotte Reinhardt, Olympia Bontems, Karine Salamin, Marina Fratti, Gabriela Blanchard, Yun-Tsan Chang, Helga Wagner, Philipp Hermann, Michel Monod, Wolfram Hoetzenecker and Emmanuella Guenova
J. Fungi 2022, 8(10), 1019; https://doi.org/10.3390/jof8101019 - 27 Sep 2022
Cited by 9 | Viewed by 2074
Abstract
Rapid and reliable fungal identification is crucial to delineate infectious diseases, and to establish appropriate treatment for onychomycosis. Compared to conventional diagnostic methods, molecular techniques are faster and feature higher accuracy in fungal identification. However, in current clinical practice, molecular mycology is not [...] Read more.
Rapid and reliable fungal identification is crucial to delineate infectious diseases, and to establish appropriate treatment for onychomycosis. Compared to conventional diagnostic methods, molecular techniques are faster and feature higher accuracy in fungal identification. However, in current clinical practice, molecular mycology is not widely available, and its practical applicability is still under discussion. This study summarizes the results of 16,094 consecutive nail specimens with clinical suspicion of onychomycosis. We performed PCR/sequencing on all primary nail specimens for which conventional mycological diagnostics remained inconclusive. In specimens with a positive direct microscopy but negative or contaminated culture, molecular mycology proved superior and specified a fungal agent in 65% (587/898). In 75% (443/587), the identified pathogen was a dermatophyte. Positive cultures for dermatophytes, yeasts and non-dermatophyte molds (NDMs) were concordant with primary-specimen-DNA PCR/sequencing in 83% (10/12), 34% (22/65) and 45% (76/169), respectively. Among NDMs, agreement was high for Fusarium spp. (32/40; 80%), but low for Penicillium spp. (5/25; 20%) and Alternaria spp. (1/20; 5%). This study underlines the improvement in diagnostic yield by fungal primary-specimen-DNA PCR/sequencing in the event of a negative or contaminated culture, as well as its significance for the diagnosis of dermatophyte and non-dermatophyte onychomycosis. Molecular mycology methods like PCR and DNA sequencing should complement conventional diagnostics in cases of equivocal findings, suspected NDM onychomycosis or treatment-resistant nail pathologies. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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13 pages, 1684 KiB  
Article
Deep Learning Assisted Diagnosis of Onychomycosis on Whole-Slide Images
by Philipp Jansen, Adelaida Creosteanu, Viktor Matyas, Amrei Dilling, Ana Pina, Andrea Saggini, Tobias Schimming, Jennifer Landsberg, Birte Burgdorf, Sylvia Giaquinta, Hansgeorg Müller, Michael Emberger, Christian Rose, Lutz Schmitz, Cyrill Geraud, Dirk Schadendorf, Jörg Schaller, Maximilian Alber, Frederick Klauschen and Klaus G. Griewank
J. Fungi 2022, 8(9), 912; https://doi.org/10.3390/jof8090912 - 28 Aug 2022
Cited by 5 | Viewed by 1981
Abstract
Background: Onychomycosis numbers among the most common fungal infections in humans affecting finger- or toenails. Histology remains a frequently applied screening technique to diagnose onychomycosis. Screening slides for fungal elements can be time-consuming for pathologists, and sensitivity in cases with low amounts of [...] Read more.
Background: Onychomycosis numbers among the most common fungal infections in humans affecting finger- or toenails. Histology remains a frequently applied screening technique to diagnose onychomycosis. Screening slides for fungal elements can be time-consuming for pathologists, and sensitivity in cases with low amounts of fungi remains a concern. Convolutional neural networks (CNNs) have revolutionized image classification in recent years. The goal of our project was to evaluate if a U-NET-based segmentation approach as a subcategory of CNNs can be applied to detect fungal elements on digitized histologic sections of human nail specimens and to compare it with the performance of 11 board-certified dermatopathologists. Methods: In total, 664 corresponding H&E- and PAS-stained histologic whole-slide images (WSIs) of human nail plates from four different laboratories were digitized. Histologic structures were manually annotated. A U-NET image segmentation model was trained for binary segmentation on the dataset generated by annotated slides. Results: The U-NET algorithm detected 90.5% of WSIs with fungi, demonstrating a comparable sensitivity with that of the 11 board-certified dermatopathologists (sensitivity of 89.2%). Conclusions: Our results demonstrate that machine-learning-based algorithms applied to real-world clinical cases can produce comparable sensitivities to human pathologists. Our established U-NET may be used as a supportive diagnostic tool to preselect possible slides with fungal elements. Slides where fungal elements are indicated by our U-NET should be reevaluated by the pathologist to confirm or refute the diagnosis of onychomycosis. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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12 pages, 1753 KiB  
Article
Alternative Splicing in Trichophyton rubrum Occurs in Efflux Pump Transcripts in Response to Antifungal Drugs
by Marcos E. R. Lopes, Tamires A. Bitencourt, Pablo R. Sanches, Maíra P. Martins, Vanderci M. Oliveira, Antonio Rossi and Nilce M. Martinez-Rossi
J. Fungi 2022, 8(8), 878; https://doi.org/10.3390/jof8080878 - 20 Aug 2022
Cited by 1 | Viewed by 1728
Abstract
Dermatophytes are challenging to treat because they have developed many strategies to neutralize the stress triggered by antifungals. Drug tolerance is achieved by mechanisms such as drug efflux and biofilm formation, and cellular efflux is a consequence of the synergistic and compensatory regulation [...] Read more.
Dermatophytes are challenging to treat because they have developed many strategies to neutralize the stress triggered by antifungals. Drug tolerance is achieved by mechanisms such as drug efflux and biofilm formation, and cellular efflux is a consequence of the synergistic and compensatory regulation of efflux pumps. Alternative splicing (AS) has also been considered as a mechanism that enhances fungal adaptive responses. We used RNA-seq data from the dermatophyte Trichophyton rubrum exposed to undecanoic acid (UDA) to search for and validate AS in genes encoding efflux pumps. The magnitude of this phenomenon was evaluated using UDA and other antifungals (caspofungin, itraconazole, and terbinafine) in planktonic and biofilm cultures. In addition to the conventional isoforms, the efflux pump encoded by TERG_04309 presented two intron-retained isoforms. Biofilms trigger the simultaneous production of at least two isoforms. The intron-retained isoforms showed short lengths and topologically different organization. Furthermore, we identified the putative interaction of efflux pumps (TERG_04309 and TERG_04224). Co-expression of these genes suggests a synergistic action in antifungal resistance. Our data provide new insights into drug tolerance related to differential isoform usage and the co-expression of stress-responsive genes, which may lead to higher antifungal resistance, mainly in biofilms. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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Review

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18 pages, 5329 KiB  
Review
Trichophyton indotineae—An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide—A Multidimensional Perspective
by Silke Uhrlaß, Shyam B. Verma, Yvonne Gräser, Ali Rezaei-Matehkolaei, Maryam Hatami, Martin Schaller and Pietro Nenoff
J. Fungi 2022, 8(7), 757; https://doi.org/10.3390/jof8070757 - 21 Jul 2022
Cited by 60 | Viewed by 8483
Abstract
Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype [...] Read more.
Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype VIII within the T. mentagrophytes/T. interdigitale species complex, which was described in 2019 by sequencing the Internal Transcribed Spacer (ITS) region of ribosomal DNA of the dermatophyte. More than 10 ITS genotypes of T. interdigitale and T. mentagrophytes can now be identified. T. indotineae causes inflammatory and itchy, often widespread, dermatophytosis affecting the groins, gluteal region, trunk, and face. Patients of all ages and genders are affected. The new species has largely displaced other previously prevalent dermatophytes on the Indian subcontinent. T. indotineae has become a problematic dermatophyte due to its predominantly in vitro genetic resistance to terbinafine owing to point mutations of the squalene epoxidase gene. It also displays in vivo resistance to terbinafine. The most efficacious drug currently available for this terbinafine-resistant dermatophytoses, based on sound evidence, is itraconazole. Full article
(This article belongs to the Special Issue Dermatophytes and Dermatophytoses)
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