Candida auris, an emerging multidrug-resistant fungal pathogen, poses a significant diagnostic and infection control challenge with limited identification methodologies. To overcome this, we developed and validated a rapid, specific, and direct colony real-time PCR assay for C. auris identification without DNA extraction. Species-specific primers were designed using comparative genomics and subjected to rigorous experimental validations. The optimized assay using a selected primer pair (Candida-auris-5F/5R) successfully identified C. auris directly from the cultured colonies within two hours. It demonstrated high specificity against eight clinically relevant non-auris Candida species, and sufficient sensitivity (as low as 100 cells/reaction) for routine laboratory testing. This method significantly reduced the turnaround time, labor, and costs compared to conventional molecular techniques that require DNA extraction. Acknowledging the recent emergence of Clade I strains in Japan, the selected primer pairs and positive controls were distributed nationally to all 59 regional public health institutes by January 2025, establishing a standardized surveillance system. This assay is expected to play a key role in timely detection of C. auris, thereby improving patient care and outbreak management.

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Invasive fungal infections (IFIs) have increased in recent years due to population aging and a rising number of immunocompromised patients. The prognosis for IFIs remains poor, making accurate diagnosis and appropriate treatment essential. Low culture positivity rates and the difficulty in distinguishing IFIs from diseases such as tuberculosis on computed tomography imaging further complicate diagnosis and may delay. We encountered a case of invasive candidiasis leading to respiratory failure, in which differentiation from miliary tuberculosis on imaging was challenging. Autopsy revealed histopathological findings of eosinophilic exudates filling the alveolar spaces and poorly stained spherical fungi. Using scanning electron microscopy and DNA extraction from formalin-fixed, paraffin-embedded (FFPE) tissues, genetic analysis identified Debaryomyces hansenii, also known as Candida famata. FFPE tissue-based analytical techniques serve as valuable tools for understanding IFIs. If the causative pathogen can be identified during a patient's life, appropriate treatment can be selected, potentially improving the prognosis of IFIs.

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Pathogenic basidiomycetes are increasingly recognized as causative agents of mycoses, particularly allergic bronchopulmonary mycosis (ABPM), in humans. To clarify their clinical significance, we analyzed the fungal species, their sources and associated diseases of 650 basidiomycetous strains preserved at the Medical Mycology Research Center, Chiba University, from 2010 to 2024. Schizophyllum commune was the most frequently isolated species (60%), followed by Trametes spp. (9.5%), Irpex spp. (5.2%), and Bjerkandera adusta (4.3%). Most isolates originated from respiratory specimens and were associated with ABPM, pneumomycosis, or sinusitis. These fungi often cannot be identified in culture because of their limited morphological characteristics. Therefore, we developed a multiplex polymerase chain reaction (PCR) assay targeting the internal transcribed spacer region for the rapid discrimination of S. commune, B. adusta, Irpex spp., and Trametes spp. Species- and genus-specific forward and reverse primers yielded distinct amplicon sizes for each target. The assay demonstrated high specificity and showed no cross-reactivity with non-target fungi; the results were concordant with those of rDNA sequencing. Multiplex PCR provides a rapid, cost-effective tool for identifying clinically important basidiomycetes, facilitating the timely diagnosis and management of fungal respiratory diseases.

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A man in his seventies without immunocompromised background presented with a slowly enlarging skin lesion on the dorsum of his right hand that had developed 6 months prior to his visit to our hospital. At the initial examination, a 3-cm brownish plaque associated with mild pain was observed on the dorsum of the right hand. Histopathological examination revealed a mass of hyphae in the subcutaneous tissue that was positive for periodic acid-Schiff and Grocott's stains. Fungal culture of the skin tissue yielded black-brown, downy colonies. Based on nucleotide sequencing of the internal transcribed spacer region and the β-tubulin gene, the organism was identified as Phaeoacremonium alvesii. After oral administration of terbinafine (TBF) at 125 mg/day was initiated, the lesions gradually improved. The strain exhibited slightly reduced sensitivity to TBF (minimum inhibitory concentration: 1 μg/mL). More than six months of oral therapy was required to achieve remission of the skin lesions. P. alvesii is a recently classified species, redefined in 2005 based on β-tubulin gene analysis, with only a few reported cases of human infection.

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Fungal pathogenesis involves several molecular mechanisms, with adhesion to host tissues being a key step that occurs through interactions between host and fungal molecules at an early stage of infection. The functions of these proteins can be better understood through protein expression analysis. However, there is a lack of commercially available antibodies or recombinant proteins against fungal molecules. Moreover, the functions of several fungal molecules remain unknown, highlighting the necessity of protein analysis to identify target proteins and elucidate their roles. Techniques such as pull-down assay, co-immunoprecipitation, and surface plasmon resonance assay are commonly used for protein interaction analysis. In this review, we describe a screening method for identifying fungal pathogenic factors using protein interaction analysis methods to investigate the interaction between the pathogenic yeast Trichosporon asahii and human molecules.

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For the treatment of hematologic diseases such as acute leukemia and lymphoma, cytotoxic chemotherapy and hematopoietic stem cell transplantation (HSCT) are often used in routine clinical practice. Fungal infections are not only associated with high mortality, but also have a significant impact on the subsequent treatment of hematologic diseases. In general, it is often difficult to make a definitive diagnosis of fungal infections in the field of hematologic diseases. In addition, it is important to accurately assess risk factors for fungal infections, monitor and diagnose, and timely select and administer antifungal medications, including prophylaxis, empiric therapy, early or preemptive therapy, and targeted therapy. The accuracy of monitoring and diagnosis of fungal infections has improved dramatically, and many new antifungal drugs have become available in Japan in recent years. Furthermore, large-scale clinical trials have provided much evidence regarding the efficacy and safety of various antifungal agents for prophylaxis, empiric therapy, early or preemptive therapy, and targeted therapy. While the number of treatment options for fungal infections has increased in recent years, it is also important to make appropriate treatment choices for fungal infections. Inappropriate use of antifungal drugs is a major problem from the perspective of fungal resistance and also from the health economics, and it is necessary to promote their appropriate use. This review focuses on evidence-based interventions for the fungal infections control associated with intensive chemotherapy for hematologic diseases and HSCT, including risk assessment, monitoring and diagnosis, prophylaxis, empiric therapy, early or preemptive therapy, and targeted therapy.

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The optimization of antifungal therapy based on pharmacokinetics/pharmacodynamics (PK/PD) principles is crucial for improving outcomes in invasive fungal infections; however, its clinical application faces considerable hurdles. This review presents a comprehensive overview of current knowledge and aims to bridge basic research and clinical practice. We outline the fundamental concepts of PK/PD and the characteristics of the major antifungal drug classes (polyenes, echinocandins, flucytosines, and azoles), along with preclinical evidence defining the main PK/PD indices (maximum concentration to minimum inhibitory concentration ratio, 24-h area under the concentration-time curve to the minimum inhibitory concentration ratio, and percentage of time the concentration remains above the minimum inhibitory concentration). Key challenges hindering translation are critically analyzed, including substantial knowledge gaps—particularly for filamentous fungi; high inter-patient pharmacokinetic variability complicating standard dosing; limitations of therapeutic drug monitoring (TDM); the narrow therapeutic window requiring careful balance between efficacy and toxicity; and the role of suboptimal exposure in antifungal resistance. Current strategies, including antifungal stewardship, are discussed, and future directions highlighted. Prioritizing research on understudied pathogens, improving TDM, developing novel agents, and strengthening collaboration between basic research and clinical practice are essential. A deeper understanding and effective application of PK/PD principles are vital to advance personalized antifungal therapies and improve patient outcomes.

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The first cases of Trichophyton tonsurans infection outbreaks were reported in Japan beginning around the turn of the 21th century. Initial reports were of group infections among high school and college combat sports athletes. Gradually, the spread of infection to younger age groups, such as junior high school students, was confirmed. Today, T. tonsurans is considered one of the major causative organisms of tinea corporis and tinea capitis in Japan. The most common clinical manifestations of T. tonsurans infection are tinea corporis and tinea capitis. Tinea corporis can be difficult to distinguish from eczema, and most cases of tinea capitis are classified as being asymptomatic carriers. These presentations can make early diagnoses challenging. Diagnosis is often established by direct microscopic examination and fungal culture to isolate and identify the causative organism. In terms of treatment, T. tonsurans infection is primarily treated using an oral antifungal therapy.
This review focuses on the status of T. tonsurans infections in Japan. T. tonsurans is an anthropophilic dermatophyte and may be difficult for the human immune system to eliminate. Hence, we must consistently keep T. tonsurans infection in mind during daily clinical practice.

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Zoonoses are generally defined as infections that are naturally transmitted between humans and other vertebrate animals. Among fungi, dermatophytes are well-established zoonotic pathogens. In contrast, many pathogenic molds are environmental saprophytes, with infections typically resulting from the direct uptake of fungal propagules—such as airborne spores—from soil, decaying organic matter, or other non-living reservoirs. Rather than being transmitted between animals and humans, these infections originate from environmental sources. In 1958, Terskikh introduced the term “sapronosis” (or “saprozoonosis”) to describe such infections acquired from the environment rather than from other living hosts. In 2003, Hubálek expanded on this concept, providing a comprehensive list of major sapronoses and their causative agents, including Aspergillus fumigatus, the primary cause of aspergillosis. Aspergillosis is a fungal disease caused by species of the genus Aspergillus, typically acquired through inhalation of airborne spores from soil and other external environments. Although the environmental transmission of Aspergillus spp. has long been recognized, recent changes in human living environments, evolving animal husbandry practices, and global ecological shifts—including climate change and the human-mediated dispersal of pathogenic organisms—highlight the need to re-evaluate these fungi as sapronotic agents. In this review, we revisit the concept of sapronosis using aspergillosis as a representative example, drawing on investigations conducted in collaboration with colleagues involving penguins housed in zoos and aquariums and the characteristics of their captive environments. Through these studies, we aim to explore the implications of environmental fungal exposure for both human and animal health.

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Dermatophytoma is a type of onychomycosis with distinctive clinical features. Clinically, it typically appears as a linear spike, triangular, or round white- or yellow-colored mass on the nail plate. Dermatophytes are thought to adhere to the nail surface and secrete extracellular polysaccharides (EPS), proteins, DNA, and other components, forming a biofilm matrix. EPS typically encases this microbial aggregation and is synthesized by the microbial constituents of the biofilm. Herein, we review dermatophytoma and the relationship between nail infection and biofilm. We also discuss green nails with dermatophytoma and infection models of biofilm formation.

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To assess the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of itraconazole (ITCZ), terbinafine (TBF), and miconazole (MCZ) in eight isolates of Microsporum canis. The MICs in the eight tested strains were < 0.03 mg/L for TBF, < 0.03 to 0.125 mg/L for ITCZ, and 1 to 4 mg/L for MCZ. The MFCs in the eight strains were 0.5 to 2 mg/L for TBF, 2 to > 32 mg/L for ITCZ, and 16 to > 32 mg/L for MCZ. These results suggested that there were strains with MFC concentrations much higher than the MIC concentrations, indicating fungistatic activity.

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