Virulence strategies from distinct phylogenetic species of the Histoplasma capsulatum complex have been scarcely documented. Using assays for intracellular replication of H. capsulatum yeasts, induction of cytokine production in yeast-infected human cell-lines (pneumocytes A549 and differentiated macrophages THP-1), and determination of lethal dose 50
This narrative review summarizes current evidence on the role of micafungin in patients with hematologic malignancies and hematopoietic stem cell transplantation (HSCT), a population at high risk for invasive fungal infections (IFIs). Micafungin, an echinocandin with activity against most Candida spp. and Aspergillus spp., is characterized by a favorable safety profile, predictable pharmacokinetics, and minimal drug–drug interactions, making it particularly attractive in patients receiving complex targeted therapies. Micafungin has a well-established role in the prevention of IFIs in selected patients with hematologic malignancies, particularly during induction chemotherapy for acute myeloid leukemia/myelodysplastic syndromes and during the pre-engraftment period after allogeneic HSCT when the local risk of invasive mould disease is low. Its use in emerging populations such as cellular-therapy and bispecific-antibody recipients should be individualized because micafungin-specific evidence remains limited. Micafungin is also an established treatment option for invasive candidiasis, although species identification, susceptibility testing, appropriate step-down therapy, and consideration of site-specific limitations are essential. Evidence supporting empirical treatment of febrile neutropenia is supportive but comparatively limited. Its role in invasive aspergillosis remains limited, mainly as salvage or combination therapy, and its lack of activity against certain moulds and rare fungi should be considered. The emergence of Candidozyma auris (C. auris) and echinocandin-resistant Candida spp. further underscores the importance of species identification, susceptibility testing, and clinical surveillance. Extended-interval and intermittent micafungin dosing may offer practical advantages and pharmacokinetic feasibility, but clinical noninferiority to daily administration has not been established and such regimens remain off-label and investigational. Overall, its optimal use requires careful patient selection and awareness of its spectrum limitations, supporting a tailored approach to antifungal management in hematologic patients.
The patient was a 26-year-old immunocompetent albino male engaged in breeding work, who presented with pruritic facial rashes for 2 months. The diagnosis was confirmed by histopathological examination, periodic acid-Schiff staining, mycological tests and gene sequencing of the lesion culture. The patient was treated with oral itraconazole combined with topical antifungal cream, and obtained complete remission without recurrence during the 8-year follow-up. This case suggests that occupational exposure can increase the susceptibility to alternariosis in immunocompetent people, and cutaneous alternariosis should be considered for refractory inflammatory facial lesions.
Rhizopus arrhizus is one of the most common etiological agents of mucormycosis worldwide, whereas Mucor irregularis has been reported with a relatively high frequency in China, exhibiting clear regional characteristics. However, the molecular basis underlying their differential host responses remains incompletely understood. Fungal extracellular vesicles (EVs) play diverse biological roles across fungal species and have emerged as important carriers of bioactive cargos that modulate host–pathogen interactions. In this study, we compared features of EVs derived from R. arrhizus and M. irregularis and evaluated their immunomodulatory effects. EVs were isolated from PBS suspensions collected from fungal cultures via differential ultracentrifugation, followed by physical and proteomic characterization. Quantitative proteomics via DIA (data independent acquisition) identified 246 EV-associated proteins showing species-specific detection or quantitative abundance differences between the two species. In the murine footpad infection model, R. arrhizus induced more severe local lesions than M. irregularis, whereas EVs from M. irregularis elicited substantially higher pro-inflammatory cytokine expression in RAW 264.7 macrophages in vitro. Collectively, our results demonstrate marked divergence between R. arrhizus and M. irregularis in EV size, protein composition, and macrophage responses, providing a comparative resource for further investigation of EV-associated factors in Mucorales-host interactions.
Talaromyces marneffei is a thermally dimorphic fungal pathogen endemic to Southeast Asia and southern China, yet chromosome-scale genomic resources from early clinical isolates remain limited. Here, we combined PacBio HiFi sequencing with Oxford Nanopore and Hi-C validation to generate a gap-free, telomere-to-telomere genome assembly of strain B33c, a 1984 clinical isolate from China. The 28.1-Mb assembly comprises eight chromosomes and enabled detailed characterization of chromosomal architecture, including chromosome termini, the repeat landscape, and putative centromeric regions. Using 3314 single-copy orthologs, we reconstructed a time-calibrated phylogeny that recovered two major lineages among the sampled T. marneffei isolates, with B33c clustering closely with the Vietnamese isolates. Comparative synteny analyses showed a largely conserved chromosome-scale backbone within T. marneffei, alongside isolate-specific rearrangement-like patterns. Orthogroup profiling revealed a widely shared gene-family repertoire with isolate-specific variation, as illustrated by differences in the functional enrichment profiles of the ATCC 18224- and B33c-specific orthogroup sets. Overall, the B33c T2T assembly expands genomic resources for T. marneffei and provides additional strain-specific information for comparative studies of genome organization and evolution.
