Alternaria species can induce multisystem infections in humans, and infections of the skin and skin structures (cutaneous alternariosis) can come in a variety of forms and be easily misdiagnosed. It is crucial to investigate the manifestation of alternariosis, the species of Alternaria spp., and susceptibility. By searching Pubmed, Wanfang, and Chinese full-text journal databases for case reports, descriptive analysis was performed to construct a database. In total, 58 publications appeared during 2010-2022 involving 74 patients were obtained. The major risk factors were organ transplantation, hematologic malignancies, trauma history, and occupational exposure. The infections were caused by ten pathogenic species, the most prevalent of which was Alternaria infectoria group (33.8%) including A. anthropophila, A. atrobrunnea, and A. guarroi, followed by A. alternata (28.4%). A. arborescens, A. chlamydospora, A. rosae, A. tenuissima, and A. triticina are less common pathogens. The predominant manifestation of the skin lesions was skin mass, including nodules, tumors, plaques, papules, etc. Granulomas is the main performance of histopathology. The fungi of this genus are susceptible to posaconazole and itraconazole. Drug-resistance of infection strains is on the rise. The manifestations of cutaneous alternariosis can simulate a variety of diseases. Few cases involving immune abnormality or deep tissue infection warrant special attention.
Cryptococcal infection often leads to fatal cryptococcal meningitis, with the primary pathogens being the Cryptococcus neoformans species complex (CNSC) and the Cryptococcus gattii species complex (CGSC). To date, at least eight cryptococcal lineages have been identified, which exhibit significant differences in geographic distribution and virulence characteristics. This review provides a detailed analysis of various molecular typing methods used in cryptococcal research, including serotyping, multi-locus enzyme electrophoresis (MLEE), pulsed-field gel electrophoresis (PFGE), random amplified polymorphic DNA (RAPD), restriction fragment length polymorphism (RFLP), PCR fingerprinting, amplified fragment length polymorphism (AFLP), multilocus microsatellite typing (MLMT), multilocus sequence typing (MLST), mass spectrometry identification (MALDI-TOF MS), and whole genome sequencing (WGS) techniques. In the future, combined application of MALDI-TOF MS, WGS and AI machine learning would improve our understandings of the epidemiological characteristics and evolutionary history of Cryptococcus, and reveal the phylogenetic patterns, origin location and transmission patterns of cryptococcal pathogens, as well as the micro-evolutionary mutations occurring within host niches, which are of great significance to clinical decisions on diagnosis and treatment of cryptococcosis.
Psoriasis is a chronic, recurrent, and refractory dermatosis. Due to impaired skin barrier function, the pathogenic fungi generally can be isolated from psoriatic lesions. With the widespread use of immunosuppressants, particularly biologics, in the treatment of psoriasis, the incidence of fungal infections in patients with psoriasis is increasing. However, the role of fungal infections in the onset, progression, and prognosis of psoriasis remains unclear, and a systematic understanding of fungal species diversity in psoriasis is lacking. In this paper, relevant literature from Medline and Chinese academic databases was systematically reviewed and analyzed, providing a comprehensive summary of the fungal species associated with psoriasis and their impact on disease burden. The fungal species reported in psoriasis include Candida spp., Trichophyton spp., Aspergillus spp., Malassezia spp., Scedosporium spp., Exophiala spp., Histoplasma spp., Cryptococcus spp., Mucor spp., Pneumocystis spp., as well as recently reported species such as Fusarium spp. and Stemphylium spp. These fungi play roles in inducing, exacerbating, and influencing the prognosis of psoriasis and may even mimic psoriatic lesions. Therefore, routine fungal infection screening was recommended before initiating immunosuppressive therapy in psoriasis patients, particularly before the use of TNF-α inhibitors, IL-17 inhibitors, and methotrexate.
This study aims at investigating whether Trichophyton mentagrophytes enhances its host adaptability through homothallic sexual reproduction. The clinical isolate JYP23487, obtained from the hair of a 3-year-old boy suffered from kerion lesion, was identified as T. mentagrophytes via ITS sequencing following purification. Morphological analysis revealed two distinct phenotypes, velvety type and granular type, with evidence of self-fertilization. After isolating these phenotypes individually, the MAT1-1-1 and MAT1-2-1 gene fragments were amplified for further analysis. Sequence chromatograms were compared, and a haplotype network diagram was constructed by referencing available data on T. mentagrophytes and related species harboring the MAT1-1-1 gene locus. Sequence comparison revealed that the granular type strain exhibited base doublets at common single nucleotide polymorphism (SNP) sites within the T. mentagrophytes complex population, indicating that this strain was heterozygous. Haplotype analysis of the MAT1-1-1 gene demonstrated that 30 strains of T. mentagrophytes and related species could be classified into four haplotypes. The heterozygous strain JYP23487k corresponded to the hypothetical intersection point between Hap 1 and Hap 2 in the haplotype networks. This finding fills a critical gap in the evolutionary continuum of the population and supports the genetic continuity inferred from haplotype analysis. The identification of this heterozygous strain provides evidence that besides colonizing and infecting humans through asexual reproduction, T. mentagrophytes also employs homothallic sexual reproduction as an adaptive strategy to explore potential host transfer and survive in diverse ecological niches.
Fungal species identification constitutes the cornerstone of medical mycology research, particularly in the diagnosis and treatment of pathogenic fungi. With the increase of diversity and quantity of clinical fungal pathogens, morphological identification has proven insufficient to meet the requirements of precise species determination. DNA barcoding, as a rapid species identification technology based on specific short genetic markers, enables accurate identification of clinical pathogens, particularly newly isolated fungal strains. This study integrated morphological characterization with DNA barcoding techniques to achieve species-level identification of 35 Penicillium strains isolated from patients with skin and skin structure fungal infections through combined phenotypic analysis and multi-locus phylogenetic assessment. As a result, these clinical isolates were classified into nine species: Penicillium allii-sativi, P. aurantiogriseum, P. brevicompactum, P. chrysogenum, P. crustosum, P. expansum, P. mexicanum, P. polonicum, and P. rubens. Of which P. allii-sativi and P. mexicanum were newly recorded in China and first globally isolated from clinical specimens. Our findings suggest that the integration of morphological and DNA barcoding approaches provides a feasible methodology for precise species-level identification of Penicillium isolates, potentially serving as a diagnostic technique for clinical identification of pathogenic Penicillium species.
Minocycline (MIN), a second-generation semi-synthetic tetracycline antibiotic, exhibits potent synergistic antifungal activity against Aspergillus fumigatus when combined with azoles. The ABCM gene (GenBank ID: AFUA_4G09150) encodes an ABC transporter protein. In this study, the ABCM knockout strain (ΔABCM) of A. fumigatus was successfully constructed. Susceptibility changes of ΔABCM and wild-type (WT) strains to MIN-triazole combinations were evaluated using in vitro antifungal susceptibility test according to the CLSI M38-A3 guideline and the disk diffusion assay. Results demonstrated that deletion of ABCM abolished the synergistic effect between MIN and posaconazole (POS), as reflected by the fractional inhibitory concentration index (FICI) values (WT: FICI=0.156 vs. ΔABCM: FICI=0.625). Disk diffusion assays revealed significantly smaller inhibition zones for the ΔABCM strain as compared with WT when treated with MIN-POS combinations (P<0.05), indicating loss of synergy upon ABCM deletion. Further investigations showed that MIN-POS treatment induced significantly lower reactive oxygen species (ROS) production in ΔABCM as compared with that in WT (P<0.05). In comparison with WT, ΔABCM exhibited higher rhodamine 6G fluorescence intensity and enhanced tolerance to oxidative stressors menadione under MIN-POS co-treatment (P<0.05). These findings suggest that the ABCM gene may serve as a critical target mediating the synergistic antifungal effects of MIN and POS, and its deletion disrupts this synergy. Additionally, ABCM gene expression may reduce external resistance. This study advances the understanding of the synergistic antifungal mechanism of MIN and azoles, offering a new theoretical foundation for elucidating A. fumigatus drug resistance.
This study explored the biological function of the ABCB1 gene (ATP-binding cassette, subfamily B, member 1, GenBank ID: 20312659) in Exophiala dermatitidis, focusing on its role in fungal growth and drug sensitivity. An ABCB1 knockout strain was constructed, and its phenotypic characteristics were systematically compared with those of the wild-type strain, including growth rate, drug sensitivity, drug efflux capacity, and intracellular ATP levels. The results demonstrated that the ABCB1 gene likely belongs to the MDR/TAP subfamily of ABC transporters and is involved in nutrient uptake and drug efflux processes. The knockout strain exhibited significantly reduction in growth rate, diminution of hyphal and conidial production, enhancement of susceptibility to azole antifungals, impairment of drug efflux capability, and decrease of intracellular ATP content. These findings indicate that the ABCB1 gene plays a crucial role in the growth and drug resistance of E. dermatitidis, suggesting its potential as a therapeutic target for novel antifungal drug development.
Early diagnosis of fungal infections is challenging. Histopathology is the gold standard for diagnosing invasive fungal diseases. To explore the value of histopathological examination in the clinical diagnosis on fungal infections, this study retrospectively analyzed 68 cases of fungal infection diagnosed by histopathology from two tertiary hospitals in Suzhou between 2015 and 2025. The analysis focused on the consistency between clinical expected diagnoses and histopathological diagnosis, description of fungi detected in histopathological terms, as well as origins of specimens and specimen types. In addition, HE staining and special fungal staining (PAS, GMS) were performed on stomach, lung and skin tissues to compare the differences in the identification of fungi by these staining methods. The results showed that only 8.8% cases were clinically expected fungal infection. Suspected fungal infection reported by histopathological detection accounted for 11.8% (8/68); fungal infection accounted for 88.2% cases (60/68); fungi identified at genus level accounted for 23.5% (16/68), including Aspergillus infection in 12 specimens from otolaryngology and 2 specimens from lung, Cryptococcus in one specimen from lung, Malassezia in one skin specimen. According to preliminary statistics, 64.7% specimens were sent from the otorhinolaryngology, and secondarily from general surgery (14.7%, 10/68). The highest rate of fungal detection were appeared in otorhinolaryngology and respiratory tract specimens. Among otorhinolaryngology specimens, 89.7% (35/39) specimens were clinically undertermined as fungal infection, while none of the 10 cases from lung were determined clinically as fungal infection. All specimens are stained by hematoxylin-eosin (HE), while only 4 specimens are specially stained by periodic acid-Schiff (PAS), accounting for 5.9% (4/68). This study compared three staining methods and demonstrated that fungal specimens could be stained red or brown by PAS and GMS, making them easier to identify and reducing the risk of missed diagnosis. It is suggested that clinicians attach importance to histopathological examination in the diagnosis of fungal infections, in order to improve the diagnosis and treatment level.
Phialophora verrucosa infection can cause phaeohyphomycosis and chromoblastomycosis, with cutaneous lesions often presenting as black proliferation. Diagnosis and treatment are particularly challenging, especially in immunocompromised patients. In this paper, a case of phaeohyphomycosis caused by P. verrucosa infection in a post-renal transplant patient is reported. The patient was a 66-year-old male farmer presenting a plaque on the lateral aspect of the right hand for four months. He underwent renal transplantation 15 years ago and had been receiving long-term oral immunosuppressive therapy with tacrolimus, mycophenolate mofetil, and prednisone. Histopathological examination revealed a large infiltration of inflammatory cells and multinucleated macrophages, along with brown, round, thick-walled spores and pigmented septate hyphae. Culture on Sabouraud dextrose agar produced black velvety colonies, and microscopic examination showed pigmented, branched, and septate hyphae. Slide cultures demonstrated phialide structures resembling bouquets; the phialides were flask-shaped or elliptical, producing oval conidia; the conidia aggregated in clusters around the phialide apex, resembling a flower. The morphological features were consistent with those of P. verrucosa. The illness was diagnosed as phaeohyphomycosis. Oral itraconazole was administered and the dose of the immunosuppressant tacrolimus was reduced. Six months later, the cutaneous lesions largely resolved. The skin lesions caused by P. verrucosa infection are usually black in color, and are often clinically misdiagnosed as malignant melanoma. Timely identification of the pathogen and initiation of antifungal therapy are critical for successful treatment, and it is essential to appropriately reduce immunosuppressive agents in renal transplant recipients.
A case of disseminated cutaneous sporotrichosis is reported in a 65-year-old male presenting with ulcerations and exudation on his extremities for over three months. The ulcers exhibited undermined borders with surrounding erythema and abundant purulent discharge at the base accompanied by severe pain. Histopathological examination revealed infectious granulomas. Fungal culture and molecular biological identification confirmed that the pathogen was Sporothrix globosa. The patient was diagnosed as disseminated cutaneous sporotrichosis.
