Diagnostic ability of Peptidase S8 gene in the Arthrodermataceae causing dermatophytoses: A metadata analysis.

An unambiguous identification of dermatophytes causing dermatophytoses is necessary for accurate clinical diagnosis and epidemiological implications. In the current taxonomy of the Arthrodermataceae, the etiological agents of dermatophytoses consist of seven genera and members of the genera Trichophyton are the most prevalent etiological agents at present. The genera Trichophyton consists of 16 species that are grouped as clades, but the species borderlines are not clearly delimited. The aim of the present study was to determine the discriminative power of subtilisin gene variants (SUB1-SUB12) in family Arthrodermataceae, particularly in Trichophyton. Partial and complete reads from 288 subtilisin gene sequences of 12 species were retrieved and a stringent filtering following two different approaches for analysis (probability of correct identification (PCI) and gene gap analysis) conducted to determine the uniqueness of the subtilisin gene subtypes. SUB1 with mean PCI value of 60% was the most suitable subtilisin subtype for specific detection of T.rubrum complex, however this subtype is not reported in members of T. mentagrophytes complex which is one of the most prevalent etiological agent at present. Hence, SUB7 with 40% PCI value was selected for testing its discriminative power in Trichophyton species. SUB7 specific PCR based detection of dermatophytes was tested for sensitivity and specificity. Sequences of SUB7 from 42 isolates and comparison with the ITS region showed that differences within the subtilisin gene can further be used to differentiate members of the T. mentagrophytes complex. Further, subtilisin cannot be used for the differentiation of T. benhamiae complex since all SUB subtypes show low PCI scores. Studies on the efficiency and limitations of the subtilisin gene as a diagnostic tool are currently limited. Our study provides information that will guide researchers in considering this gene for identifying dermatophytes causing dermatophytoses in human and animals.

Dual quantitative PCR assays for the rapid detection of Trichophyton indotineae from clinical samples.

Trichophyton indotineae is an emerging species of the Trichophyton mentagrophytes complex (TMC), responsible for an epidemic of widespread hairless skin infections that is frequently (50-70%) resistant to terbinafine. In order to initiate appropriate treatment as quickly as possible without waiting for culture positivity (10-15 days) and molecular identification from the strain, we developed a dual quantitative PCR (qPCR) for the direct detection of T. indotineae in clinical samples. We first designed a T. indotineae-specific qPCR assay (TI-qPCR) targeting a single specific polymorphism in the internal transcribed spacer region. Although none of the 94 non-dermatophyte and 7 dermatophyte species were amplified, this TI-qPCR allowed amplification of other TMC species at a lower yield. With equal amounts (0.1 ng) of DNA per reaction, the mean quantitative cycle (Cq) values for T. indotineae and non-indotineae TMC were 27.9 (±0.1) and 38.9 (±0.3), respectively. Therefore, we normalized this assay against a previously validated pan-dermatophyte qPCR assay (PD-qPCR) and relied on the ΔCq [(TI-qPCR) - (PD-qPCR)] to identify T. indotineae versus other TMC species. Dual assay was validated using 86 clinical samples of culture-confirmed T. indotinea and 19 non-indotineae TMC cases. The mean ΔCq for non-indotineae TMC was 9.6 ± 2.7, whereas the ΔCq for T. indotinea was -1.46 ± 2.1 (P < .001). Setting the ΔCq at 4.5 as a cutoff value resulted in 100% specificity for the detection of T. indotineae. This dual qPCR assay quickly detects T. indotineae from skin scrapings, aiding in early diagnosis and treatment for patients with suspected infection.

Identifying the emerging species Trichophyton indotineae is long and requires to wait for culture positivity. We developed a dual qPCR strategy to detect T. indotineae directly from clinical sample with a 100% sensitivity.

Potential emergence of terbinafine resistance by squalene epoxidase gene mutations: An 18-month cohort study of onychomycosis patients in the United States.

BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.

Molecular Detection of Dermatophytes and Nondermatophytes in Onychomycosis in Antalya, Turkey.

BACKGROUND: Onychomycosis is a chronic nail infection, and dermatophytes, yeasts, and nondermatophytic molds may be the causative agents. This study aimed to determine the etiological agents of onychomycosis by using conventional and molecular methods. METHODS: Between June 2020 and July 2021, 37 patients with a presumptive diagnosis of onychomycosis and mycological evidence (culture and/or EUROArray Dermatomycosis assay) were included in the study. Organisms detected in cultured nail specimens were identified by combined phenotypic characteristics and by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). An EUROarray Dermatomycosis assay was used for molecular detection of fungal pathogens. RESULTS: The EUROArray Dermatomycosis assay was positive for a single fungal target in 23 samples, and 14 samples were positive by culture. The most common pathogen was Trichophyton rubrum in both methods. Coinfection was detected in 14 samples by using molecular methods, and Trichophyton rubrum and Fusarium solani (9 samples) were the most common pathogens detected together. Trichophyton spp., nondermatophyte molds, and Candida spp. were detected in 33 (89.2%), 16 (43.2%), and 6 (16.2%) samples, respectively, when the two methods were evaluated together. CONCLUSIONS: Our results revealed that fungal culture allows the diagnosis of onychomycosis, but it is not as sensitive as the EUROArray Dermatomycosis test, especially in patients receiving antifungal therapy.

Terbinafine-resistant T. indotineae due to F397L/L393S or F397L/L393F mutation among corticoid-related tinea incognita patients.

Tinea incognita (TI) can mimic other dermatoses, presenting a diagnostic challenge for dermatologists. In some uncertain cases, it is crucial to accurately identify the causative agent using internal transcribed spacer (ITS) sequencing. The global issue of drug-resistant dermatophytosis is increasing, with Trichophyton (T.) indotineae being the main cause. This study presents four cases of TI (diagnosed as eczema) by terbinafine-resistant T. indotineae strains and reviews the current global TI epidemiology based on geographical continent and related conditions. Furthermore, squalene epoxidase (SQLE)-associated resistance mechanisms are evaluated. Lesions caused by terbinafine-resistant T. indotineae strains do not respond to allylamine antifungals, thus allowing the infection to spread. Among T. indotineae isolates, the SQLE F397L substitution is the most prevalent mutation contributing to azole resistance. F397L and L393F replacements in SQLE were detected in all isolates that exhibited high-level resistance. L393S was seen in isolates with low-resistant strains. Interestingly, and for the first time, an L393F amino acid substitution in the SQLE gene product was detected in the Iranian clinical T. indotineae strain. Also, a genomics-based update on terbinafine resistance that focuses on T. indotineae is discussed in this study.

Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae.

Importance: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission. Objective: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing. Design, Setting, and Participants: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers. Main Outcome and Measure: Improvement or resolution at the last follow-up assessment. Results: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 µg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates. Conclusion and Relevance: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

INTRODUCTION: The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. METHODS: A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. RESULTS AND DISCUSSION: A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. CONCLUSION: Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Clinico-mycological and therapeutic updates on cutaneous dermatophytic infections in the era of Trichophyton indotineae.

Trichophyton indotineae has emerged as a novel dermatophyte species resulting in treatment recalcitrant skin infections. While the earliest reports came from India, T. indotineae has now spread to many parts of the world and is rapidly becoming a global health concern. Accurate identification of T. indotineae requires elaborate mycological investigations which is beyond the domain of routine microbiology testing. Extensive, non-inflammatory and atypical presentations are commonly seen with this novel species. T. indotineae shows an alarmingly high rate of mutations in the squalene epoxidase gene leading to lowered in vitro susceptibility to terbinafine. This has also translated into a lowered clinical response and requirement of a higher dose and much longer durations of treatment with the drug. Although the species remains largely susceptible to itraconazole, prolonged treatment durations are required to achieve cure with itraconazole. Fluconazole and griseofulvin do not have satisfactory in vitro or clinical activity. Apart from requirement of prolonged treatment durations, relapse postsuccessful treatment is a distressing and yet unexplained consequence of this "species-shift." Use of third generation azoles and combinations of systemic antifungals is unwarranted as both have not demonstrated clear superiority over itraconazole given alone, and the former is an important class of drugs for invasive mycoses.

New thymol-derived triazole exhibits promising activity against Trichophyton rubrum.

Fungal infections have emerged worldwide, and azole antifungals are widely used to control these infections. However, the emergence of antifungal resistance has been compromising the effectiveness of these drugs. Therefore, the objective of this study was to evaluate the antifungal and cytotoxic activities of the nine new 1,2,3 triazole compounds derived from thymol that were synthesized through Click chemistry. The binding mode prediction was carried out by docking studies using the crystallographic structure of Lanosterol 14α-demethylase G73E mutant from Saccharomyces cerevisiae. The new compounds showed potent antifungal activity against Trichophyton rubrum but did not show relevant action against Aspergillus fumigatus and Candida albicans. For T. rubrum, molecules nº 5 and 8 showed promising results, emphasizing nº 8, whose fungicidal and fungistatic effects were similar to fluconazole. In addition, molecule nº 8 showed low toxicity for keratinocytes and fibroblasts, concluding that this compound demonstrates promising characteristics for developing a new drug for dermatophytosis caused by T. rubrum, or serves as a structural basis for further research.

Resistance Profile, Terbinafine Resistance Screening and MALDI-TOF MS Identification of the Emerging Pathogen Trichophyton indotineae.

The emerging pathogen Trichophyton indotineae, often resistant to terbinafine (TRB), is known to cause severe dermatophytoses such as tinea corporis and tinea cruris. In order to achieve successful treatment for these infections, insight in the resistance profile of T. indotineae strains and rapid, reliable identification is necessary. In this research, a screening medium was tested on T. indotineae strains (n = 20) as an indication tool of TRB resistance. The obtained results were confirmed by antifungal susceptibility testing (AST) for TRB following the in vitro broth microdilution reference method. Additionally, AST was performed for eight other antifungal drugs: fluconazole, itraconazole, voriconazole, ketoconazole, griseofulvin, ciclopirox olamine, naftifine and amorolfine. Forty-five percent of the strains were confirmed to be resistant to terbinafine. The TRB resistant strains showed elevated minimal inhibitory concentration values for naftifine and amorolfine as well. DNA sequencing of the squalene epoxidase-encoding gene showed that TRB resistance was a consequence of missense point mutations in this gene, which led to amino acid substitutions F397L or L393F. MALDI-TOF MS was used as a quick, accurate identification tool for T. indotineae, as it can be challenging to distinguish it from closely related species such as Trichophyton mentagrophytes or Trichophyton interdigitale using morphological characteristics. While MALDI-TOF MS could reliably identify ≥ 95% of the T. indotineae strains (depending on the spectral library), it could not be used to successfully distinguish TRB susceptible from TRB resistant strains.

[Trichophyton mentagrophytes genotype VII increasingly causes anogenital infections]. / Trichophyton mentagrophytes Genotyp VII als zunehmender Auslöser anogenitaler Infektionen.

In the course of globalization, migration and global warming, we are increasingly confronted with pathogens that do not occur naturally in our latitudes or appear in a different form. We know keratinophilic dermatophytes as the cause of tinea pedis, onychomycosis and also tinea corporis and capitis. Transmission usually occurs via domestic or farm animals and via autoinoculation. In recent years dermatophytes have gained additional importance as a possible sexually transmitted disease between immunocompetent persons. For the first time, dermatophytosis was described as a sexually transmitted infection in travelers who developed pronounced pubogenital or anogenital tinea after travelling in Southeast Asia, including Thailand, mostly after intensive sexual contact. Molecular and cultural analyses have identified Trichophyton (T.) mentagrophytes ITS (internal transcribed spacer) genotype VII as the main pathogen. Although this dermatophyte genotypically belongs to the zoophilic complex, direct (sexual) and occasionally indirect human-to-human contact with infected persons is suspected to be the current route of transmission. The infection can lead to inflammatory and purulent dermatophytosis, causing a high level of suffering. In this respect, a rapid and reliable diagnosis is essential in order to be able to initiate targeted treatment. The discovery of infection pathways and the awareness of the need to take rare diseases into account in our everyday lives will increasingly accompany us over the next few years and present us with new challenges, particularly in terms of prevention and treatment.

[Conventional and molecular diagnostics in onychomycosis-part 2 : Molecular identification of causative dermatophytes by polymerase chain reaction and sequence analysis of the internal transcribed spacer region of ribosomal DNA]. / Konventionelle und molekulare Diagnostik bei Onychomykose ­ Teil 2 : Molekulare Identifizierung der ursächlichen Dermatophyten mit Polymerasekettenreaktion und Sequenzanalyse der ITS("internal transcribed spacer")-Region der ribosomalen Desoxyribonukleinsäure.

Dermatophyte identification using traditional methods such as optics-based direct fluorescence microscopy and culture is nowadays supplemented by molecular biological methods. The validity of dermatophyte DNA detection with direct uniplex-polymerase chain reaction-enzyme immunoassay (PCR-EIA) in nail samples was proven by sequence analysis of the ribosomal internal transcribed spacer (ITS) region. A total of 108 dermatophytes, isolated from patients with onychomycosis, were positive for Trichophyton rubrum (TR) and Trichophyton interdigitale (TI) in culture and/or uniplex-PCR-EIA. Conventional methods for dermatophyte identification were complemented by direct uniplex-PCR-EIA and sequence analysis of the ribosomal ITS region (18S rRNA, ITS1, 5.8S rRNA, ITS2, 28S rRNA). Of 108 patients (average age 62, median age 73), 56 showed cultural growth with 31 of them being identified as TR and 23 as TI. There was high agreement with the sequence analysis. Surprisingly, the pathogen of a single nail sample was identified as T. quinckeanum (formerly T. mentagrophytes sensu stricto), a rare zoophilic dermatophyte in Germany. A single TI strain turned out to be a misidentified T. tonsurans based on the sequence analysis. In all, 34 of the 52 specimens lacking cultural growth were detected by PCR as TR, and 18 specimens could be identified as TI. The results of dermatophyte identification of culture-negative nail samples were also in agreement with the results of sequence analysis. Molecular biological methods are well applicable, and they show high reliability for direct dermatophyte identification in nail samples without prior cultivation. Especially for nail samples without cultural growth, PCR-based dermatophyte identification was highly specific and sensitive.

Deep dermatophytosis caused by Trichophyton rubrum in an elderly patient with CARD9 deficiency: A case report and literature review.

Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.

Deep-seated dermatophytosis caused by Trichophyton rubrum in patient with Becker muscular dystrophy.

Trichophyton rubrum is a common fungal pathogen that usually causes superficial infection limited to epidermis only, so called dermatophytosis. However in immunocompromised patients, dermatophytosis can be exceptionally more invasive with extensive lesions involving deep tissues and generating sometimes systemic course. We report the case of a 43-year-old heart transplanted man, who presented with multiple deep-seated nodules and papules in the inguinal areas and in the buttocks. Involvement of Trichophyton rubrum was confirmed by culture, DNA sequencing and histological examination that showed granulomatous inflammatory infiltrates with the presence of hyphae in the dermis. Antifungal therapy with oral terbinafine for four weeks was successful; in spite of initial remnant atrophic scars, the lesions were completely cleared after four month evolution. Deep-seated invasive dermatophytosis is rare, but should be considered with immunocompromised conditions, especially when history of previous superficial dermatophytosis is present.

Severe kerion Celsi caused by Trichophyton quinckeanum: Severe kerion Celsi due to Trichophyton quinckeanum.

We report a severe case of kerion Celsi of the scalp in a previously healthy 13-year-old girl due to Trichophyton quinckeanum, an emerging dermatophyte species in Europe. The species was definitely identified by DNA sequencing and the patient was successfully treated by oral terbinafine for 6 weeks. Kerion Celsi is a severe inflammatory form of tinea capitis, which is characterised by a purulent discharge and alopecia [1]. It typically occurs in children infected with zoophilic dermatophytes, such as Trichophyton mentagrophytes, and an increasing number of cases caused by other Trichophyton species has recently been reported [2]. Herein we report a severe case of kerion Celsi of the scalp caused by the emerging species Trichophyton quinckeanum, which was successfully treated by oral antifungal.

Development of an agar-based screening method for terbinafine, itraconazole, and amorolfine susceptibility testing of Trichophyton spp.

Resistance in dermatophytes is an emerging global public health issue. We, therefore, developed an agar-based method for screening Trichophyton spp. susceptibility to terbinafine (TRB), itraconazole (ITC), and amorolfine (AMF) and validated it using molecularly characterized isolates. Α total of 40 Trichophyton spp. isolates, 28 TRB wild type (WT) (13 T. rubrum, 10 T. mentagrophytes, 5 T. interdigitale) and 12 TRB non-WT (7 T. rubrum, 5 T. indotineae) with different alterations in the squalene epoxidase (SQLE) gene, were used. The optimal test conditions (inoculum and drug concentrations, incubation time, and temperature) and stability over time were evaluated. The method was then applied for 86 WT Trichophyton spp. clinical isolates (68 T. rubrum, 7 T. interdigitale, 6 T. tonsurans, 5 T. mentagrophytes) and 4 non-WT T. indotineae. Optimal growth of drug-free controls was observed using an inoculum of 20 µL 0.5 McFarland after 5-7 days of incubation at 30°C. The optimal concentrations that prevented the growth of WT isolates were 0.016 mg/L of TRB, 1 mg/L of ITC, and 0.25 mg/L of AMF, whereas 0.125 mg/L of TRB was used for the detection of Trichophyton strong SQLE mutants (MIC ≥0.25 mg/L). The agar plates were stable up to 4 months. Inter-observer and inter-experimental agreement were 100%, and the method successfully detected TRB non-WT Trichophyton spp. strains showing 100% agreement with the reference EUCAST methodology. An agar-based method was developed for screening Trichophyton spp. in order to detect TRB non-WT weak and strong mutant isolates facilitating their detection in non-expert routine diagnostic laboratories.

PCR-based methods in detection and identification of dermatophytes in dogs and cats with suspected dermatophytosis in 2021 in Poland.

Dermatophytes from Microsporum, Trichophyton and Epidermophyton genera are divided into geophilic, zoophilic and anthropophilic species which cause skin infection in humans and wide group of animals, mainly mammals. Main species causing dermatophytosis in dogs and cats are Microsporum and Trichophyton. Conventional mycological diagnostic technique includes Saburaud Dextrose Agar (SAD) and others medium cultures, 10% KOH mount and direct microscopy of hairs and scraping. Molecular diagnostic become more frequent in veterinary practice due to shortening of waiting time. In this study we based on two PCR methods. The nested PCR amplified CHS1 gene for dermatophytes detection, and multiplex PCR coding ITS1 and ITS2 fragments for species identification of detected derpatophytes. Most frequently detected species was Microsporum canis, mainly in young cats. Geophilic Microsporum gypseum and anthropophilic Trichophyton rubrum was found primarily in dogs. Molecular methods in dermatophytosis identification are rapid in contrast to routinely, long lasting culture.

Erythroderma combined with deeper dermal dermatophytosis due to Trichophyton rubrum in a patient with myasthenia gravis: first case report and literature review.

BACKGROUND: Dermatophytes are the most common causative pathogens of mycoses worldwide and usually cause superficial infections. However, they can enter deep into the dermis lead to invasive dermatophytosis such as deeper dermal dermatophytosis on rare occasions. Erythroderma is a severe dermatological manifestation of various diseases resulting in generalized skin redness, but erythroderma due to fungi infections is barely reported. In this article, we reported the first case of erythroderma combined with deeper dermal dermatophytosis due to Trichophyton rubrum (T. rubrum) in a patient with myasthenia gravis. CASE PRESENTATION: A 48-year-old man was hospitalized because of erythema with scaling and nodules covering his body for a month. The patient had a history of myasthenia gravis controlled by regularly taking prednisolone for > 10 years and accompanied by onychomycosis and tinea pedis lasting > 8 years. Based on histopathological examinations, fungal cultures, and DNA sequencing results, the patient was finally diagnosed with dermatophyte-induced erythroderma combined with deeper dermal dermatophytosis caused by T. rubrum. After 2 weeks of antifungal treatment, the patient had recovered well. CONCLUSIONS: This case report shows that immunosuppressed patients with long histories of superficial mycoses tend to have a higher risk of developing invasive dermatophytic infections or disseminated fungal infections. Dermatologists should be alert to this condition and promptly treat the superficial dermatophytosis.

TrCla4 promotes actin polymerization at the hyphal tip and mycelial growth in Trichophyton rubrum.

IMPORTANCE: Superficial fungal infections, such as athlete's foot, affect more than 10% of the world's population and have a significant impact on quality of life. Despite the fact that treatment-resistant fungi are a concern, there are just a few antifungal drug targets accessible, as opposed to the wide range of therapeutic targets found in bacterial infections. As a result, additional alternatives are sought. In this study, we generated a PAK TrCla4 deletion strain (∆Trcla4) of Trichophyton rubrum. The ∆Trcla4 strain exhibited deficiencies in mycelial growth, hyphal morphology, and polarized actin localization at the hyphal tip. IPA-3 and FRAX486, small chemical inhibitors of mammalian PAK, were discovered to limit fungal mycelial proliferation. According to our findings, fungal PAKs are interesting therapeutic targets for the development of new antifungal medicines.

Genomic Analysis of Antifungal Drug Resistance Induced in Trichophyton rubrum After Prolonged Culture with Terbinafine.

In this study, we induced terbinafine (TRF) resistance in a T. rubrum strain in vitro for 18 months then compared the genomes of the TRF-resistant (N42-3) and TRF-susceptible wild-type (N42WT) strains to identify mutations. In the SQLE gene, N42WT had no mutation while N42-3 had a F397L mutation. We sequenced approximately 22.53 Mb of the genomes of the N43WT and N42-3 strains. Other than the F397L mutation in SQLE, there were three other genetic mutations in three different genes that were found in N42-3, but not in N43WT; however, these three mutations were not detected in other TRF-resistant T. rubrum strains. From this genome sequencing analysis, the only variation that was confirmed to be associated with drug resistance in the genome of the TRF-resistant T. rubrum was a hotspot mutation in SQLE.