The evolutionary closely related dermatophytes Trichophyton rubrum and T. violaceum exhibit distinct pathobiology despite high genomic similarity, suggesting the involvement of epigenetic regulation beyond genetic determinants. This study aimed to delineate the genome-wide DNA methylation landscapes of T. rubrum and T. violaceum and to elucidate the associations between epigenetic divergence, transcriptional programs, and pathogenic disparities. We performed an integrated multi-omics analysis combining whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) on clinical isolates of both species. Systematic bioinformatic analyses were performed to identify differentially methylated regions (DMRs), differentially expressed genes (DEGs), and to explore their potential functional associations. T. rubrum exhibited a significantly elevated global DNA methylation level (mean ± SD: 3.21

ABSTRACT Dermatophytosis is a highly prevalent superficial fungal infection, yet antifungal susceptibility testing results remain difficult to interpret because clinical breakpoints are unavailable, and epidemiological cutoff values (ECVs) are still limited for most dermatophyte–drug combinations. We conducted a multicenter study of 305 Trichophyton mentagrophytes and Trichophyton interdigitale isolates collected between 2019 and 2024 at six tertiary hospitals across geographically diverse regions of China. Antifungal susceptibility testing was performed using the CLSI M38 broth microdilution method under standardized quality control, and provisional ECVs were derived following CLSI M57 guidance. For T. mentagrophytes, fluconazole showed a non-unimodal MIC distribution and was not assigned a provisional ECV. The remaining seven agents yielded ECVs of 1 µg/mL for ciclopirox olamine and griseofulvin, 0.5 µg/mL for itraconazole, 0.06 µg/mL for voriconazole, 0.25 µg/mL for posaconazole and amorolfine, and 0.016 µg/mL for terbinafine. For T. interdigitale, fluconazole showed a complex non-unimodal distribution, whereas itraconazole and posaconazole showed unstable low-MIC shoulders precluding ECV estimation. The remaining five agents yielded ECVs of 1 µg/mL for ciclopirox olamine, 0.25 µg/mL for griseofulvin, 0.12 µg/mL for voriconazole and amorolfine, and 0.016 µg/mL for terbinafine. Isolates above the provisional ECVs were uncommon for most combinations (≤2.5%), except for griseofulvin against T. interdigitale (20.5%). Overall, the two species showed distinct MIC distribution profiles, underscoring the value of species-level analysis and continued surveillance. These multicenter CLSI-based data and provisional ECVs provide a contemporary baseline for species-specific interpretation of dermatophyte susceptibility data in China.IMPORTANCEReliable interpretation of dermatophyte antifungal susceptibility testing remains limited because clinical breakpoints and epidemiological cutoff values (ECVs) are unavailable for most dermatophyte–drug combinations. This is particularly important for the Trichophyton mentagrophytes/Trichophyton interdigitale species complex, which is increasingly implicated in refractory dermatophytosis and may display species-specific susceptibility patterns. In this multicenter study, we established provisional epidemiological cutoff values for most tested species–agent combinations and showed that these two closely related species differ in MIC distribution profiles and in the detection of non-wild-type isolates. These data provide practical laboratory thresholds for recognizing isolates with reduced susceptibility, highlight the limitations of complex-level interpretation, establish a contemporary baseline for dermatophyte susceptibility surveillance in China, and may help support laboratory-informed antifungal decision-making.

BACKGROUND:Trichophyton indotineae is an emerging dermatophyte associated with extensive inflammatory tinea and terbinafine resistance. Routine laboratory methods often fail to distinguish T indotineae from related lineages in the Trichophyton mentagrophytes-interdigitale complex, hindering surveillance and delaying resistance testing. We aimed to define the public internal transcribed spacer (ITS) haplotypes of T indotineae and develop novel molecular assays for accurate identification. METHODS:We conducted a marker identification and assay validation study by recurating GenBank ITS records (annotated as T mentagrophytes, T interdigitale, and T indotineae) from database inception to March 10, 2026, and performing haplotype analysis based on a 540 bp ITS region. We excluded records lacking complete coverage of this region or containing degenerate bases or alignment gaps from the primary network. We analysed Trichophyton genomes to identify a T indotineae-specific single-copy marker, OG7443, and developed duplex endpoint PCR and TaqMan real-time PCR assays. These assays were validated using culture isolates and direct skin-scraping specimens across two centres in China and one in the Netherlands. FINDINGS:Of 5584 ITS records retrieved, 4744 were retained for haplotype analysis after curation. The type-associated haplotype H002 comprised 1576 records, and a type-strain-anchored T indotineae cluster comprised 1698 records across 75 haplotypes. Duplex endpoint PCR identified all T indotineae and non-T indotineae isolates (sensitivity 100% [57/57; 95% CI 93·7-100·0]; specificity 100% [105/105; 96·5-100·0]). The TaqMan assay identified all culture isolates and direct skin scrapings, with sensitivity 100% (53/53; 93·3-100·0) and specificity 100% (160/160; 97·7-100·0). Estimated consumable costs were US$0·39 per sample for duplex endpoint PCR and $4·24 for TaqMan PCR. INTERPRETATION:OG7443 is a species-specific genomic marker for T indotineae that supports two assay formats. These assays could aid surveillance, case recognition, and triage for downstream resistance testing, but direct-specimen performance requires confirmation in larger prospective cohorts. FUNDING:Noncommunicable Chronic Diseases-National Science and Technology Major Project; Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; 111 Project; Brazilian Council for Scientific and Technological Development.

BACKGROUND:The emergence of Trichophyton indotineae as a multidrug-resistant dermatophyte has challenged conventional therapeutic approaches for dermatophytosis, leading to a significant therapeutic dilemma. The absence of formal epidemiological cutoff values (ECVs) under the Clinical and Laboratory Standards Institute (CLSI) framework has led to inconsistent interpretation of antifungal susceptibility testing (AFST) data, highlighting the urgent need for standardised susceptibility interpretation criteria and effective therapeutic strategies. OBJECTIVES:This study aimed to (1) establish CLSI-based estimated tentative ECVs (ET-ECVs) to facilitate reliable minimum inhibitory concentration (MIC) interpretation; (2) analyse resistance rates of T. indotineae to terbinafine, itraconazole and voriconazole using a large-scale global dataset and (3) explore and identify effective therapeutic options following first-line treatment failure. METHODS:This systematic review compiled global susceptibility data for T. indotineae through comprehensive literature searches, including only studies that performed CLSI- or European Committee on Antimicrobial Susceptibility Testing (EUCAST)-standardised AFST. Furthermore, the clinical efficacy of voriconazole was specifically evaluated by summarising and analysing reported treatment cases. RESULTS:A total of 67 studies from 14 countries, comprising 981 isolates, were included. The proposed CLSI ET-ECVs for terbinafine, itraconazole and voriconazole were 0.125, 0.25 and 1 mg/L, respectively, showing full alignment with EUCAST tentative epidemiological cutoff values (TECOFFs). Integrated resistance rates were 77.6% for terbinafine, 17.0% for itraconazole and 1.4% for voriconazole. Cross-resistance analysis revealed that terbinafine resistance predominated, with 14.3% of isolates co-resistant to itraconazole. In vitro susceptibility data demonstrated high activity of voriconazole and clinical case summaries further confirmed its favourable therapeutic efficacy, with complete remission reported in all evaluated cases. CONCLUSION:This study defined the CLSI ET-ECVs for interpreting T. indotineae MICs, highlighted the resistance burden to first-line agents and provided in vitro evidence supporting further evaluation of voriconazole as a potential effective alternative therapy. These findings may provide critical warnings regarding the high-resistance landscape and help guide antifungal susceptibility interpretation for this emerging multidrug-resistant pathogen.

Invasive pulmonary fungal diseases (IPFD) continue to posing an increasing clinical and public health burden on immunocompromised populations. In many Asian settings, the diagnosis of IPFD faces substantial challenges driven by the high prevalence of comorbidities, including poorly controlled diabetes, tuberculosis (TB), and human immunodeficiency virus (HIV) infection, considerable heterogeneity in local pathogens, and disparities in access to diagnostic resources. To address these unmet needs, experts from 18 countries collaboratively developed this consensus, which provides a diagnostic algorithm tailored to high-burden Asian settings based on existing international and regional guidelines. When clinical manifestations are atypical or diagnostic clues are limited, the algorithm prioritizes evaluation for common and regionally prevalent IPFD, followed by stepwise expansion to other potential fungal pathogens. In addition, this consensus outlines the regional accessibility of different diagnostic modalities across Asia. This consensus focuses exclusively on optimization of the diagnostic algorithm and does not provide specific recommendations regarding antifungal therapy. Notably, improved diagnosis of IPFD through this algorithm may contribute to better patient outcomes and strengthened public health strategies in high-burden regions.

The emergence and spread of antifungal-resistant Trichophyton indotineae pose an increasing public health concern worldwide. Multidrug-resistant T. indotineae infections have been reported in China in the past few years. To understand the genetic relationship and the origin of these Chinese isolates, as well as their relationship to the global collections, we sequenced the whole genomes of 31 isolates using the Illumina platforms. Genomic epidemiology was performed on a dataset of 181 T. indotineae isolates from China and 8 other countries, representing the largest genome-wide analysis. Single nucleotide polymorphism analysis revealed that T. indotineae can be divided into four distinct phylogenetic groups (I, II, III, IV), with regional clonal transmission clusters identified in eastern China; T. indotineae was introduced into China more than once given the genetic variability. The isolates from South Asia may be the source of Chinese isolates based on epidemiological information. There were differences in the prevalence and resistance profiles among four phylogenetic groups, with Group III being predominant and exhibiting a higher terbinafine resistance rate of 88.24% and azole resistance. Also, we characterized the role of gene mutation, copy number variation, and gene expression in antifungal drug resistance. Terbinafine resistance could be mainly associated with Phe397Leu substitution in SQLE, and azole resistance might be related to increased copy number of CYP51B, as well as elevated MDR2 and MDR3 expression. Given the clinical challenges posed by T. indotineae, this emerging dermatophyte should be recognized as a global threat, necessitating urgent collaborative surveillance and management strategies.

BACKGROUND:Trichophyton mentagrophytes ITS genotype VII (TMVII) has recently been identified as a cause of genital infections, raising concerns about its potential as an emerging sexually transmitted pathogen. However, the epidemiology and clinical features of TMVII infection remain poorly understood. OBJECTIVES:To systematically review published TMVII cases and characterise its demographic distribution, transmission patterns, clinical manifestations and treatment outcomes. METHODS:A comprehensive literature review was conducted, including all published molecularly confirmed TMVII cases. Data on demographics, infection sites, co-infections and treatments were extracted and analysed. RESULTS:A total of 124 TMVII cases from 10 studies were included. Among 60 cases with detailed clinical data, tinea genitalis (36.7%) and tinea faciei/barbae/capitis (51.7%) were the common infection types. TMVII infection predominantly affected men who have sex with men (64%), with high co-infection rates of HIV (29.6%) and gonorrhoea (42.6%). Most cases were reported in France (49%) and Germany (35%), suggesting possible local transmission. Oral terbinafine (250 mg/day for 4-8 weeks) achieved a 64.4% cure rate (38/59 courses), while limited data indicated itraconazole and griseofulvin were also effective. Fluconazole showed no therapeutic efficacy. CONCLUSION:TMVII can be transmitted through sexual activities, particularly affecting MSM and individuals with concomitant STDs. Current evidence suggests that oral terbinafine is effective, meanwhile other antifungals need further observation. Increased focus is warranted on the clinical management and monitoring of TMVII infection.

The worldwide emergence of Trichophyton indotineae has garnered significant attention due to its growing resistance to conventional antifungal therapies, posing significant challenges to the effective management of dermatophytosis. The in vitro activities of 16 antifungals were tested against 37 T. indotineae isolates using the broth microdilution method according to Clinical and Laboratory Standards Institute protocol M38-A3. Luliconazole and amorolfine exhibited low MICs, while itraconazole showed moderately decreased susceptibility, making them preferred treatment options. Echinocandins demonstrated favourable in vitro activity against T. indotineae, but their potential as therapeutic alternatives for recalcitrant dermatophytosis remains uncertain due to pharmacokinetic and pharmacodynamic limitations. In contrast, terbinafine, fluconazole, griseofulvin, oteseconazole, isavuconazole, ravuconazole, and amphotericin B exhibited elevated MICs for many strains, with strong correlations between certain azoles, indicating potential cross-resistance. A difference in the susceptibility to terbinafine and voriconazole between Chinese and Indian isolates was observed. These findings could provide valuable insights into antifungal resistance patterns and help guide treatment strategies for T. indotineae infections. IMPORTANCE:Trichophyton indotineae is a novel emerging dermatophyte that has rapidly spread globally in recent years. Its resistance to first-line antifungal agents, particularly terbinafine and fluconazole, has significantly limited treatment options, emphasizing the urgent need for alternative therapies. This study provides comprehensive antifungal susceptibility data for 16 available antifungal agents, offering valuable insights into potential treatment strategies.

Mucor irregularis, an emerging causative agent of disfiguring mucormycosis, demonstrates distinct clinical manifestations between hyphae and spore forms, though the pathogenic determinants between these two forms remain elusive. Utilizing TMT (tandem mass tag)-based quantitative proteomics (ProteomeXchange: PXD055430), we conducted a comparative analysis of these morphotypes, followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein-protein interaction network construction. Critically, we identified the following: (i) tRNA sulfur modification (NCS6) in spore dormancy maintenance; (ii) adenylate kinase (adenylate kinase 1)-mediated energy metabolism during germination; and (iii) COQ3-dependent mitochondrial function in spore germination. This first proteomic profiling of M. irregularis morphotypes delineates distinct phase-specific adaptations. Notably, the ribosomal and dormancy-associated machinery as NCS6 in spores contrasts sharply with the metabolic activation and upregulated virulence determinants as PAC1 in hyphae. Findings highlight NAT10 critical for spore readiness and RhoGEF GTPases central to hyphal invasion as particularly promising candidate therapeutic targets. Building upon this foundation, future investigations must now delineate the immunomodulatory roles of these effector proteins during host invasion to advance mucormycosis management strategies.

BACKGROUND:Dermatophytosis caused by the Trichophyton mentagrophytes/T. interdigitale species complex (TMTISC) has attracted global attention, with increasing reports of terbinafine-resistant T. indotineae in China. OBJECTIVES:This study aims to evaluate the epidemiological features of antifungal-resistant TMTISC in China and monitor the prevalence of T. indotineae. METHODS:A total of 230 TMTISC strains were isolated from nine tertiary hospitals across three economic regions of China. These isolates were identified through molecular sequencing and phylogenetic analysis. Additionally, in vitro antifungal susceptibility testing (AFST) was performed for eight drugs, following the EUCAST 11.0 protocol. Mutations in the squalene epoxidase (SQLE) gene were detected. RESULTS:The phylogenetic tree revealed that 120 strains (52.17%) were T. mentagrophytes, 92 (40.0%) were T. interdigitale, and 18 (7.83%) were T. indotineae. Eight different genotypes were identified, including TM-IX, which was predominant in China, along with two newly discovered genotypes, TM-XXX and TM-XXXI. Among T. mentagrophytes isolates, tinea faciei (44.17%) was the common clinical type, primarily isolated from the central region. T. interdigitale isolates were mainly found in onychomycosis (36.96%), T. indotineae was commonly isolated from tinea corporis (94.44%) and tinea cruris (55.56%). AFST showed that all isolates of T. interdigitale and T. mentagrophytes were susceptible to terbinafine [minimum inhibitory concentrations (MICs) < 0.125 mg/L] and voriconazole (MICs < 0.5 mg/L). All isolates of T. indotineae were resistant to terbinafine (0.25 to >4.0 mg/L), exhibiting a single amino acid substitution in SQLE (Phe397Leu, Leu393Ser or Phe415Cys). Additionally, elevated MICs were observed in TMTISC for itraconazole, miconazole, ciclopirox (1-2 mg/L) and griseofulvin (1-64 mg/L). CONCLUSIONS:The TMTISC was predominantly composed of T. mentagrophytes, followed by T. interdigitale and T. indotineae. A rising trend of reduced azoles susceptibility in TMTISC and multi-drug resistance among T. indotineae isolates has been observed in China.

Trichophyton indotineae is a recently identified dermatophyte species that has emerged as a causative agent of chronic, treatment-refractory dermatophytosis, predominantly manifesting as tinea cruris or generalised tinea corporis. As of 2025, infections have been reported in more than 40 countries worldwide. Morphologically indistinguishable from the T. mentagrophytes complex, T. indotineae requires identification through mass spectrometry or molecular sequencing. Its genomic structure and virulence profile are highly similar to those of the T. mentagrophytes complex, with limited single nucleotide polymorphism diversity among global isolates. A hallmark of T. indotineae is its frequent resistance to terbinafine, primarily mediated by amino acid substitutions—Phe397Leu, Leu393Phe, or Leu393Ser—in the squalene epoxidase enzyme. Multidrug resistance, including reduced susceptibility to fluconazole, itraconazole, posaconazole, and griseofulvin, has also been observed, particularly among Chinese isolates. Although the mechanisms underlying azole resistance are not fully elucidated, increased copy number of the CYP51B gene has been implicated. Oral itraconazole, administered at high doses or over extended courses, currently represents a preferred therapeutic option. The global spread and antifungal resistance profile of T. indotineae present a growing threat to public health, underscoring the urgent need for enhanced surveillance, resistance monitoring, and effective clinical management strategies.

OBJECTIVES:This study reports the first isolation of a multidrug-resistant Trichophyton rubrum strain in China, characterizing its drug resistance profile and mechanisms. METHODS:The isolate was identified by internal transcribed spacer (ITS) sequencing and phylogenetic analysis. In vitro antifungal susceptibility testing (AFST) was performed according to the M38-A3 CLSI guideline to determine minimum inhibitory concentrations (MICs) against eight antifungals (terbinafine, itraconazole, fluconazole, amorolfine, griseofulvin, voriconazole, luliconazole and amphotericin B). Whole genome sequencing (WGS), transcriptome sequencing and qRT-PCR were performed to explore the resistance mechanism. RESULTS:The multidrug-resistant T. rubrum strain L-6424 was isolated from a Chinese patient with generalised tinea corporis/cruris, tinea unguium and tinea manuum. It exhibited elevated MICs to terbinafine (2 mg/L), itraconazole (0.5 mg/L), and amorolfine (0.5 mg/L). The phylogenetic tree based on genome-wide single nucleotide polymorphisms (SNPs) showed L-6424 is not a novel genotype of T. rubrum, with high genetic similarity (99.94%) with the reference strain (CBS 139224). There were three amino acid substitutions in the squalene epoxidase (SQLE), including the previously reported F397L and H440Y, as well as a newly discovered V105M, and one amino acid substitution in the CYP51A (R239C) was identified. Also, significant differences at the transcriptome level between the drug-resistant and sensitive strains were observed, and it was screened and found that CYP51A, TruMDR5 and TERG_08139 may be related to azole resistance. CONCLUSIONS:Drug-resistant T. rubrum has emerged in China, indicating the possibly increasing severity of antifungal resistance. The complex mechanism of multidrug-resistant dermophytes poses challenges to clinical treatment, needing more attention.

We describe 14 cases of native refractory dermatophytes caused by Trichophyton indotineae diagnosed at a hospital in China since 2021, primarily diagnosed in the past 1 year and from the same province. Trichophyton indotineae isolates were resistant to multiple antifungals and harboured Phe397Leu or Leu393Ser substitutions in the squalene epoxidase enzyme. Short-term rapid emergence of multidrug-resistant T. indotineae in China poses increasing threats to public safety and warrants continued public health surveillance.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membrane. It is a rare and severe disease resulting from autoimmune defects or immune dysregulations. Nonetheless, the diagnosis and treatment of CMC still pose significant challenges. Erroneous or delayed diagnoses remain prevalent, while the long-term utility of traditional antifungals often elicits adverse reactions and promotes the development of acquired resistance. Furthermore, disease relapse can occur during treatment with traditional antifungals. In this review, we delineate the advancements in molecular diagnostic and therapeutic approaches to CMC. Genetic and biomolecular analyses are increasingly employed as adjuncts to clinical manifestations and fungal examinations for accurate diagnosis. Simultaneously, a range of therapeutic interventions, including Janus kinase (JAK) inhibitors, hematopoietic stem cell transplantation (HSCT), cytokines therapy, novel antifungal agents, and histone deacetylase (HDAC) inhibitors, have been integrated into clinical practice. We aim to explore insights into early confirmation of CMC as well as novel therapeutic options for these patients.

Non-albicans Candida (NAC) species are increasingly recognized as significant contributors to candidemia infections; however, relatively less is known about the immune responses induced by these species. In this study, we compared the cytokine production ability of human peripheral blood mononuclear cells (PBMCs) upon stimulation with different Candida species (Candida spp.). We measured secreted cytokines using ELISA and checked the functional profiles of T-cell responses using multicolor flow cytometry. Although there was a differential expression of cytokines against Candida spp., significant difference were observed in the levels of IFN-γ, TNF-α, IL-10, IL-12p40, and IL-23 (p < 0.05) between Candida spp. A significant difference was observed between C. albicans and C. glabrata (p = 0.026) in the levels of TNF-α. C. glabrata showed significant differences compared to C. albicans, C. parapsilosis, and C. krusei in the levels of IL-10 (p values of 0.02, 0.04, and 0.01, respectively). Despite the percentages of CD4+ and CD8+ expressing Th1, Th2, and Th17 cytokines being higher in stimulated PBMCs, none of the Candida spp. showed significant differences. The levels of secreted IL-17A and IL-23 were consistently lower in Candida spp. regardless of the stimulus used. Here, we showed the differential regulation of Th1, Th2, and Th17 during Candida spp. stimulation of the immune system ex vivo. Additionally, our findings suggest that C. albicans elicits an IFN-γ response, whereas C. glabrata promotes IL-10 cellular responses, but this warrants additional studies to conclude this association. This investigation holds the potential to advance our comprehension of the distinct immune responses induced by Candida spp., with probable implications in designing antifungal immunotherapeutics.

Introduction: Tinea of vellus hair is a rare dermatophytosis, caused by dermatophyte infection in the vellus hair. The clinical symptoms of tinea of vellus hair are more serious and the conventional topical treatment are often ineffective. Here, we report a case of tinea of vellus hair caused by Trichophyton violaceum in a child. Case presentation: A 7-year-old boy presented with a localized, scaly, and itchy erythema on his left cheek for two months. He once used a topical corticosteroid but without any clinical improvement, the erythema was progressively enlarging and spread to the left eyebrow. He denied any contact with animals. Direct microscopy found abundant spores and hyphae on the vellus hair; T. violaceum was identified by culture and PCR examination. The patient was diagnosed with tinea of vellus hair and cured after treating with oral terbinafine 125 mg/day and topical treatment for two weeks. There was no recurrence during the follow-up period. Discussion: The clinical symptoms of tinea of vellus hair are often atypical and easy to be misdiagnosed. Timely fungal examination is necessary for suspicious patients and confirmed patients should be treated with oral antifungal drugs. Conclusion: The diagnosis and treatment of tinea of vellus hair need to be paid more attention in clinical works.

This case report describes a man in his 40s who presented with a 5-month history of recurrent pruritic papular erythema with mild scaling on the face, left forearm, and groin.

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal-Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.