Search Results (219)

The increasing prevalence of dermatophytosis and biofilm-associated infections highlights the need for new therapeutic approaches. This study evaluated the potential of Lavandula stoechas subsp. luisieri essential oil against clinically relevant dermatophytes. The essential oil obtained by hydrodistillation was chemically characterized by gas chromatography–mass spectrometry (GC–MS). Antifungal activity was assessed through determination of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), while antibiofilm activity against Epidermophyton floccosum was evaluated by measuring biofilm biomass, extracellular matrix (ECM) deposition, and cell viability. An ex vivo model of Trichophyton rubrum-induced skin infection was used to assess efficacy under tissue-relevant conditions. The essential oil was mainly composed of oxygenated monoterpenes, with trans-α-necrodyl acetate (19.1%), lavandulyl acetate (13.6%), camphor (8.8%), 1,8-cineole (6.1%), and trans-α-necrodol (5.3%) as major constituents. The oil exhibited antifungal activity against all tested dermatophytes (MIC: 12.5–100 μg/mL), induced hyphal morphological alterations, significantly inhibited E. floccosum biofilm formation, particularly ECM deposition, and reduced fungal dissemination in the ex vivo skin model. These findings support the antidermatophytic and antibiofilm potential of L. stoechas subsp. luisieri essential oil, although further studies are required. Full article

Background: Subungual malignant melanoma (SMM) is an uncommon but potentially life-threatening neoplasm that frequently mimics benign nail disorders, particularly onychomycosis. Although misdiagnosis of SMM as fungal infection is well documented, laboratory-confirmed coexistence of onychomycosis and melanoma within the same nail unit is exceedingly rare and remains insufficiently characterized in the literature. Methods: A two-patient case series is presented in which both individuals underwent comprehensive clinical evaluation, nail unit biopsy, histopathologic examination with special staining, and molecular and/or mycologic testing. Longitudinal follow-up was obtained to evaluate clinical course and outcomes. Results: Both patients presented with chronic hallux nail dystrophy and laboratory-confirmed onychomycosis. In each case, fungal infection was confirmed, however, persistent symptoms prompted subsequent biopsies, that revealed malignant melanoma. In Case 1, a 71-year-old man with Candida parapsilosis onychomycosis underwent an initial nail unit biopsy demonstrating at least melanoma in situ with ulceration. Repeat biopsy confirmed invasive melanoma with an approximate Breslow thickness of 1.0 mm, while final pathology following partial hallux amputation revealed residual ulcerated melanoma with a Breslow thickness of 2.1 mm, negative margins, and negative sentinel lymph nodes, consistent with Stage IIB disease. In Case 2, an 88-year-old woman with dermatophytic onychomycosis consistent with Trichophyton species had an initial fragmented biopsy demonstrating invasive subungual melanoma with an estimated Breslow thickness of 0.6 mm. Final pathology following distal hallux amputation confirmed residual acral melanoma with a Breslow thickness of 0.6 mm, no ulceration, a mitotic rate of less than 1/mm², and negative margins, consistent with pT1a disease. Factors contributing to delayed melanoma recognition differed between cases: prior trauma, delayed intervention, and chronic ulceration complicated Case 1, whereas treatment for presumed onychomycosis without improvement delayed suspicion in Case 2. Conclusions: These findings demonstrate that positive mycologic results do not exclude concurrent melanoma and underscore the potential for diagnostic anchoring bias, supporting early biopsy consideration in refractory or atypical nail dystrophy. Full article

Background: Tinea capitis remains one of the most common superficial fungal infections in children worldwide and represents an important public health concern due to its high prevalence, potential complications, and changing epidemiology. This study aimed to characterize the epidemiological trends and etiological distribution of tinea capitis across the Americas through a systematic review of the available literature. Methods: A systematic search was conducted in MEDLINE (PubMed), Scopus, SCILIT, and SciELO following PRISMA guidelines. A total of 250 records were identified, of which 75 duplicates were removed. After title and abstract screening and eligibility assessment, 90 studies were included. Observational studies, prevalence studies, case series, and case reports reporting epidemiological or etiological data on tinea capitis in countries of the American continent were considered eligible. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. No formal certainty-of-evidence assessment or meta-analysis was performed due to the descriptive nature and heterogeneity of the included studies. This review was not prospectively registered. Results: The 90 included studies comprised 506,086 reported cases of tinea capitis. Marked regional differences were identified in the distribution of dermatophyte species. Trichophyton tonsurans predominated in North America and several Caribbean countries, whereas Microsporum canis was the most frequently reported etiological agent in much of South America and parts of Central America, suggesting an important role of zoonotic transmission in these regions. Variations in prevalence and species distribution were also associated with geographic, socioeconomic, and demographic factors. Overall, the included studies demonstrated low-to-moderate methodological risk of bias. Conclusions: These findings demonstrate substantial heterogeneity in the epidemiology of tinea capitis throughout the Americas and highlight the importance of continuous surveillance, accurate mycological diagnosis, and region-specific public health strategies to improve disease control and guide appropriate therapeutic interventions. Full article

Background/Objectives: Verbena officinalis has long been used in traditional medicine for treating skin disorders, yet its potential in advanced wound-dressing systems remains insufficiently explored. This study aimed to characterize V. officinalis extracts obtained using different solvents, evaluate their antimicrobial, antibiofilm, cytotoxic, and wound-healing activities, and develop electrospun polycaprolactone–polyethylene glycol (PCL–PEG) nanofibers as a delivery platform for the most active extract. Methods: Extracts were chemically characterized by LC–MS and evaluated against clinical bacterial, yeast, and dermatophyte isolates associated with skin infections. Antibiofilm activity was assessed against Staphylococcus lugdunensis. The most active hydroalcoholic extract (EW7.5) was incorporated into PCL–PEG nanofibers (1–10%, w/w). Metabolite release was monitored by semi-quantitative LC–MS analysis. Cytotoxicity and wound-healing activity were evaluated using HaCaT keratinocytes, while in vivo efficacy was assessed in a full-thickness excisional wound model in Dark Agouti rats (five animals per group in two independent experiments). Results: EW7.5 exhibited the strongest antimicrobial activity, with MIC values of 0.06 mg/mL against all tested bacterial and Candida strains and 0.06–0.5 mg/mL against dermatophytes. It inhibited S. lugdunensis biofilm formation by 79.43% at MIC/4 and reduced pre-formed biofilm biomass by 64.98% at 2 × MBC. EW7.5 and EW7.5-loaded nanofibers showed no cytotoxicity up to 400 μg/mL. In the scratch assay, the free extract achieved 42.34 ± 1.58% wound closure, while nanofibers containing 10% EW7.5 achieved 25.87 ± 2.52%, compared to 7.73 ± 0.07% for the control. In vivo, EW7.5-loaded membranes significantly accelerated wound closure and the 10% formulation significantly improved extracellular matrix deposition and vascular remodeling compared to the control membrane. Conclusions: EW7.5-loaded PCL–PEG nanofibers combine antimicrobial, antibiofilm, biocompatible, and wound-healing properties, supporting their potential as multifunctional wound dressings. Nevertheless, further studies with mechanistic investigations are required to fully establish their therapeutic applicability. Full article

Dermatophytosis is a cutaneous mycosis caused by keratinolytic fungi, classified as dermatophytes, affecting 20–25% of the global population and representing a significant public health concern. The disease manifests as circular, erythematous, pruritic, and desquamative skin lesions, hair breakage and loss, and nail degradation, leading to considerable morbidity. In addition, dermatophytosis can markedly impair patients’ quality of life. Despite the high global prevalence of dermatophytosis, the causative agents are often misdiagnosed, and there is limited data on the epidemiology and genomic surveillance of dermatophytosis worldwide. This review aims to update the global epidemiology of dermatophytosis and dermatophytes while addressing their taxonomy, pathogenesis, virulence factors, clinical manifestations, and antifungal therapy. Consistently, Trichophyton spp., particularly T. rubrum, T. mentagrophytes, and T. interdigitale, remain the predominant pathogens worldwide. Recently, T. indotineae has gained prominence due to its global dissemination, significant terbinafine resistance, extensive lesions, therapeutic failure, and recurrence. Furthermore, studies have reported endogenous cases of T. indotineae infections in Asia and Europe, and exogenous reports in the Americas and Oceania. Among non-Trichophyton dermatophytes, Microsporum canis and M. audouinii stand out as relevant pathogens, particularly in endemic regions and specific clinical settings, such as scalp infections. Overall, these factors emphasize the importance of global vigilance regarding dermatophyte dissemination. This review also highlights a discrepancy between accurate fungal identification and global reporting, raising concerns regarding epidemiological surveillance and underscoring the need for improved strategies to manage dermatophytosis worldwide. Full article

Dermatophytosis caused by Trichophyton spp. represents a growing public health concern, exacerbated by the increasing prevalence of difficult-to-treat infections and the emergence of resistance to standard antifungal agents, such as terbinafine. In this study, we evaluated the in vitro antifungal activity of a thiosemicarbazide derivative, 1-[(1-methyl-4-nitroimidazol-2-yl)carbonyl]-4-(3-methylphenyl)thiosemicarbazide, against a panel of anthropophilic and zoophilic Trichophyton spp. dermatophytes. Susceptibility testing was performed via the broth microdilution method to determine the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs). The compound demonstrated antifungal efficacy against all the strains tested, with MIC values ranging from 31.25 to 125 µg/mL. Crucially, low MFC/MIC ratios (≤4) confirmed a fungicidal effect, which was further corroborated by microscopic analysis revealing severe hyphal damage in treated dermatophytes. The derivative exhibited consistent activity against both T. rubrum and T. mentagrophytes, including clinical isolates. To our knowledge, this is one of the first detailed evaluations of a nitroimidazole–thiosemicarbazide hybrid against Trichophyton spp. that combines quantitative MIC/MFC testing with morphological assessment. The tested thiosemicarbazide derivative noticeably decreased the viability of VERO and A375 cells, but even at the highest tested concentration, after 72 h of incubation, the cellular viability remained at 65%. These findings suggest that the investigated compound is a promising candidate for the development of new fungicidal drugs or disinfectants for the effective prophylaxis or management of superficial mycoses in human and veterinary medicine. Full article

Sexually transmitted infections (STIs) remain a global health burden. Beyond classical pathogens, dermatophytes are increasingly identified within sexually linked transmission networks. Genital dermatophytosis is a superficial fungal infection of the genital area, primarily caused by anthropophilic and zoophilic dermatophytes. Recently, Trichophyton mentagrophytes genotype VII and Trichophyton indotineae have emerged as clinically significant dermatophytes, increasingly linked to human-to-human and sexually associated transmission within highly interconnected sexual networks. These infections are often marked by inflammatory, persistent, and treatment-refractory presentations, with prominent genital involvement and rising antifungal resistance—particularly to terbinafine—posing growing diagnostic and therapeutic challenges. Doxycycline post-exposure prophylaxis (Doxy-PEP) has recently emerged as a novel preventive strategy for bacterial STIs, involving the administration of 200 mg doxycycline within 24–72 h after activities associated with increased infection exposure, particularly among men who have sex with men (MSM) and transgender women. While effective in reducing infections such as syphilis and chlamydia, its broader implementation raises concerns regarding antimicrobial resistance. Chemsex is an increasingly prevalent behavioural phenomenon, defined as the intentional use of psychoactive substances during sexual activity to enhance or prolong the experience, particularly among MSM. It is associated with multiple adverse effects, including increased STI transmission, substance dependence, drug toxicity, psychological disturbances, and significant challenges in treatment adherence and healthcare engagement. This review aims to provide a comprehensive and clinically oriented overview of emerging trends in STIs, with a particular focus on dermatophyte infections as pathogens with potential sexually associated transmission, alongside evolving prevention strategies and behavioral factors influencing transmission. Full article

Deep dermatophytosis is a rare, life-threatening fungal infection characterised by the invasion of dermatophytes beyond the superficial layers of keratinised tissue into the dermis and subcutaneous tissues. The present review aimed to identify the current knowledge on the role of Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in the pathogenesis, clinical spectrum, diagnosis, and management of deep dermatophytosis. For innate immune activation, CARD9 acts as an adaptor molecule. Basically, CARD9 helps mediate the connection between the fungal pattern recognition receptor (Dectin-1) and the NF-κB and MAPK signalling pathways, and it mediates cytokine production, thereby activating phagocytic activities. Thereby, any change or mutation in the CARD9 gene may disrupt these pathways, leading to dysfunctional neutrophils and impaired Th17-mediated antifungal immunity. Clinically, patients with CARD9 deficiency are immunocompetent but susceptible to recurrent and/or severe fungal infections [Candida, dermatophytes (Trichophyton spp.), and phaeohyphomycetes]. Deep dermatophytosis in these patients is usually chronic, treatment-resistant, and characterized by erythematous papules, nodules, plaques, ulcers, or necrotic lesions, most of which occur on the lower limbs. It usually occurs in adulthood and is more common in males. There have been instances of geographic clustering of CARD9 deficiency in Asia, North Africa, and the Middle East. Early recognition and genetic diagnosis of CARD9 mutations in patients with recurrent or atypical deep dermatophytosis. Although antifungal therapy is essential, hematopoietic stem cell transplantation can be a definitive treatment for selected patients with CARD9 deficiency. Thus, CARD9 deficiency is a critical factor in the better management of patients but remains an underrecognized cause of severe, treatment-resistant deep dermatophytosis, and early genetic diagnosis is essential for guiding targeted management and improving patient outcomes. This review emphasises the importance of CARD9 in antifungal immunity and underscores the need for greater clinical awareness and the incorporation of genetic evaluation into the management of deep dermatophytosis. Full article

Fungal infections pose diagnostic challenges in both human and veterinary medicine, as traditional detection methods such as fungal culture are time-consuming, microscopy is operator-dependent, and molecular detection assays often require specialized instrumentation and trained personnel, which can limit their routine clinical application. This study developed a sandwich immunoassay to detect β-1,3- and β-1,6-glucans, two major components of the fungal cell wall, based on two catalytically inactive glucanase mutants, LamA_E175Q and Neg1_E321Q. The sandwich ELISA exhibited higher detection sensitivity than conventional ITS-based PCR for Saccharomyces cerevisiae and Candida albicans under the conditions of this study. Using pre-coated plates, the sample-processing and detection workflow can be completed in approximately 40 min. It effectively detected a wide range of fungal species, including yeasts (Saccharomyces cerevisiae, Candida albicans) and filamentous fungi such as dermatophytes and non-dermatophyte molds. In a preliminary clinical cohort, the assay identified β-glucan signals in all 21 samples confirmed positive for dermatophytes, while no signal was detected in 20 negative samples, suggesting potential clinical applicability. This dual-enzyme sandwich immunoassay provides a rapid and low-cost complementary tool for broad-spectrum fungal screening, which may help guide further confirmatory diagnostics and timely clinical decision-making. Full article

This study evaluates the antifungal activity of Lippia gracilis Schauer essential oil traditionally used in northeastern Brazil for the treatment of skin disorders. The essential oil isolated from fresh leaves collected in Ceará, Brazil, was chemically characterized by GC–MS, showing a thymol-dominant profile (37.52%), accompanied by p-cymene (12.13%), γ-terpinene (9.29%), and gurjunene (10.95%). Antifungal assays revealed significant activity against several dermatophyte species with MIC and MFC values ranging from 50 to 100 μg/mL. Biofilm assays against Epidermophyton floccosum demonstrated strong inhibitory effects by disrupting biofilm formation, altering fungal morphology, and promoting in vitro skin cells migration, while also showing effective preventive effects in an ex vitro nail infection model. These findings support the potential of L. gracilis essential oil as a multifunctional natural antifungal agent for the management of refractory dermatophytosis and onychomycosis, and provide scientific validation for its traditional use in skin infection treatment. Full article

Background: Superficial fungal infections caused by dermatophyte and non-dermatophyte species are increasing globally. While several comorbid diseases and risk factors have been associated with fungal infections at the individual level, their epidemiological relationships at the population level remains poorly characterized. Objective: We aimed to examine population-level associations between the burden of superficial fungal infections and selected comorbid conditions and risk factors, stratified by age, sex and country. Methods: We obtained years lived with disability (YLDs) for superficial fungal infections, diabetes, psoriasis, and atopic dermatitis and summary exposure values (SEVs) for high body mass index (BMI) and high alcohol intake from Global Burden of Disease Study 2023. Data were obtained for Australia, Brazil, the United Kingdom and the United States for males and females younger than 20 years, 20 to 54 years and 55+ years old. Pearson correlation coefficients were calculated between fungal infection YLDs and each comorbid condition (YLDs) and risk factor (SEVs). Results: Significant positive correlations were observed between superficial fungal infection burden and diabetes (R = 0.6–0.98), high BMI (R = 0.75–0.95), psoriasis (R = 0.59–0.96), and atopic dermatitis (R = 0.51–0.93) in older adults (55 years+). Correlations with high alcohol consumption were more variable across regions and sex. In young–middle-aged adults (20–54 years), moderate-to-strong correlations (R ~ 0.8–0.9) were observed, although patterns were less consistent across countries. In individuals < 20 years, associations were generally weaker, with some positive correlations observed for atopic dermatitis (R = 0.4–0.7) in select countries. Conclusions: The findings demonstrate population-level associations between superficial fungal infections and metabolic, inflammatory, and behavioural risk factors, with stronger correlations observed in older age groups. These patterns may reflect shared demographic, epidemiologic, and clinical patterns across conditions. Full article

A commercially available nitric oxide (NO)-releasing solution (NORS) has demonstrated in vitro efficacy for dermatophytosis, but a NO-releasing gel (NORG) may be more suitable for patient self-application. We present a preliminary investigation of NORS for tinea pedis and an in vitro investigation of NORG for dermatophyte infection, to complement the existing published data and expand support for a possible role of NO formulations in superficial dermatophyte infection. In vitro usage of NORS and NORG is reviewed. The antifungal efficacy of NORG was assessed via time-kill assays, zone of inhibition tests with synthetic dermal membrane permeation, and scanning electron microscopy. A randomized, controlled pilot study of NORS for tinea pedis investigated the safety and efficacy of treatment over three consecutive days, with a day-31 follow-up. The NORG demonstrated rapid fungicidal activity against T. rubrum and T. mentagrophytes and effective dermal membrane penetration while retaining antifungal action. Significant morphological damage to fungal cells was noted, indicating possible fungicidal activity. The clinical NORS treatment reduced the clinical symptom severity score by 67% on average, with no significant safety findings. These findings, in addition to existing publications, support NO-releasing formulations as potential therapies that warrant further clinical investigation for superficial fungal infection. Full article

Rapid responses to environmental changes are essential for maintaining fitness. In pathogenic fungi such as the dermatophyte Trichophyton interdigitale, appropriate responses to environmental shifts determine successful infection. Transcriptional regulation and alternative splicing (AS) are key modulators of fungal adaptation and pathogenesis. Here, we validated the role of the transcription factor PacC in coordinating AS in T. interdigitale grown in infection-mimicking medium. RNA-seq analysis of a ΔpacC mutant revealed a predominance of intron retention events, mainly involving introns 1 and 2, indicating defective splicing and potential nonsense-mediated decay of genes related to ion transport, metabolism, and genome maintenance. These alterations compromised energy balance, ergosterol biosynthesis, and cellular homeostasis. PacC-dependent AS generated alternative isoforms of cytoskeletal and metabolic proteins, including myosin-1 and a GH3 β-glucosidase, potentially modulating enzymatic activity, metabolic burden, and cell wall remodeling during infection. Exon-skipping in the chromatin remodeler RSC1 suggests PacC involvement in epigenetic regulation under host-mimicking conditions. Transmission electron microscopy revealed possible Woronin bodies, cytoplasmic disruption, and cell wall thinning in the mutant. Overall, PacC integrates transcriptional and post-transcriptional regulation to promote adaptation, survival, and virulence, highlighting AS as a regulatory layer linking environmental sensing to metabolic and epigenetic plasticity in pathogenic fungi. Full article

Dermatophytosis is a common zoonotic fungal infection in companion animals, most frequently caused by Microsporum canis, while the geophilic species Nannizzia gypsea may occasionally infect cats. Conventional morphological identification of dermatophytes is often challenging due to phenotypic similarities, underscoring the importance of molecular confirmation. In this study, dermatophyte field isolates obtained from cats with suspected dermatophytosis were identified using cultural characteristics and Internal Transcribed Spacer (ITS) region sequencing. Phylogenetic analysis based on ITS sequences showed that the isolates were highly similar to each other and clustered closely with reference strains and previously reported dermatophyte strains from different geographical regions. Subsequently, the in vitro antifungal activity of a propolis extract collected from the Muğla region (Türkiye) was evaluated using the agar dilution method at concentrations ranging from 6.25 to 100 mg/mL. At all tested concentrations, propolis inhibited mycelial growth in all four molecularly confirmed dermatophyte field isolates, whereas substantial growth was observed in the negative control plates. These findings indicate that Muğla propolis exhibits in vitro antifungal activity at the tested concentrations against dermatophyte field isolates and warrants further investigation as a potential natural antifungal source. Full article

Dermatophytes are fungi that infect the human skin and its appendages. With new pathogenic species emerging and resistance to first-line drugs rising, microbiologic diagnosis and species identification are becoming even more important. In this study, the DermaGenius^® 2.0/3.0 Complete multiplex real-time PCR and the EUROArray Dermatomycosis kits were compared to fungal culture and with each other; 78 reference strains and 124 clinical samples were analyzed. Both the DermaGenius^® kit (97%; 95%CI 89–100%) and the EUROArray assay (91%; 95% CI: 82–96%) were sensitive when analyzing on-panel reference strains. In clinical samples, the DermaGenius^® assay provided a positive result in 63 out of 124 (51%) samples and the EUROArray assay in 74 out of 124 (60%) samples. Both kits supported the diagnosis and species identification of culture-negative samples, and samples with growth of unconventional species. However, there was suspicion of false-positive results with F. solani in the EUROArray kit both in clinical and reference strains. The most common conventional dermatophytes in this study combining all methods were T. rubrum/soudanense (n = 40) and T. interdigitale/mentagrophytes (n = 11). In summary, both PCR kits were sensitive for the diagnosis and species identification of dermatophytoses. Combining culture and a PCR-based method can increase the diagnostic yield and compensate for the weakness of the other methods. The optimal PCR-based kit, and especially the optimal panel size, depends on the local epidemiology of dermatophytes. Full article