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.
Sporothrix brasiliensis is the predominant etiological agent of sporotrichosis in Brazil and has been progressively expanding its geographic distribution to other countries in South America. The human patients infected with S. brasiliensis usually respond favorably to antifungal therapy. However, therapeutic failure may occur, and management may be particularly challenging in cases of severe disease. We recently reported that at least seven S. brasiliensis genotypes circulate across South America. However, their biological and clinical relevance of this genetic diversity remains poorly understood. In this study, we investigated whether distinct S. brasiliensis genotypes are associated with reduced susceptibility to the main antifungal agents used in the treatment of human and animal sporotrichosis. A total of 92 clinical, veterinary, and environmental S. brasiliensis strains from Brazil, Paraguay and Argentina, genotyping them using a four-gene MLST scheme. Mating type was assessed as well as antifungal susceptibility according to the M38-A2 CLSI guidelines. Results were interpreted according to the established epidemiological cutoff values for S. brasiliensis. The isolates are clustered into six distinct genotypes, with mating type showing a strong association with phylogenetic clades. Non-wild type strains were identified across four haplotypes (H1, H2, H3 and H4) for all antifungal drugs tested. These non-wild type strains were isolated from six distinct Brazilian states and were not associated to a specific genetic background. Nevertheless, non-wild-type strains were predominantly detected among feline isolates, most of which originated from Minas Gerais and belonged to haplotype H2. However, because only a limited number of H2 isolates were included in this study, additional isolates from this haplotype are need to confirm this association. Together, these findings suggest that decreased antifungal susceptibility in S. brasiliensis is not genotype-restricted but may be influenced by host-related or epidemiological factors, particularly in the context of feline sporotrichosis.
Terbinafine resistance in dermatophytes is an increasing global concern, driven in part by the intercontinental spread of Trichophyton indotineae. The current epidemic of dermatophyte resistance is primarily attributed to clinical and community factors, including inappropriate antifungal use and fixed-dose corticosteroid–antifungal combinations. However, environmental antifungal contamination has emerged as a potential but largely unexplored contributor to resistance selection, as has been proposed for azole resistance in other fungal pathogens. Here, we examine whether environmental terbinafine contamination represents an overlooked One Health selection pressure or, alternatively, an exposure signal whose relevance to dermatophyte resistance remains ecologically constrained. Terbinafine is highly lipophilic, partitions into organic matter, and has been detected in wastewater, sludge, biosolids, surface water, groundwater, and sediment. Reported concentrations vary markedly by region and sample type, and in some cases exceed proposed resistance-selection thresholds. However, most clinically important dermatophytes, particularly anthropophilic Trichophyton lineages, are host-associated keratinophilic fungi rather than free-living environmental saprobes. Therefore, environmental terbinafine is unlikely to drive resistance unless viable dermatophyte propagules, keratinous substrates, and biologically active drug residues co-occur in the same ecological niche. Current evidence is insufficient to determine whether environmental terbinafine contamination contributes meaningfully to dermatophyte resistance selection. While infected wildlife and geophilic dermatophytes may serve as useful sentinel systems, they do not yet establish a causal environmental pathway for the emergence or spread of resistant T. indotineae. In order to address these knowledge gaps, we propose that future One Health surveillance should integrate terbinafine quantification with dermatophyte recovery, resistance-marker detection (i.e., SQLE screening), susceptibility testing, and experimental selection studies in biologically plausible reservoirs.
