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MYCOPATHOLOGIA · 2025 ·Vol. 190 ·期 5 ·1-13 · IF 2.9

First Isolation of a Multi-azole-Resistant Aspergillus fumigatus cyp51A TR46/Y46F/F70L Mutant in a Patient with Fungal Keratitis

Han Xiang,Zhang Heng,Mao Yuqi,Ling Wenhao,Ge Lu,Tang Menghua,Sun Yi,Wu Zhiqin

Introduction Fungal keratitis (FK), a severe ocular infection caused primarily by Fusarium spp. and Aspergillus spp., remains a major cause of blindness worldwide. Current treatment relies on antifungal agents, though emerging azole resistance in Aspergillus fumigatus complicates therapeutic outcomes. Materials and methods We isolated a clinical FK strain and assessed its antifungal susceptibility using broth microdilution and E-test methods, followed by sequencing of the cyp51A gene’s promoter region and coding sequence (CDS) to identify resistance-associated mutations. Results The isolate, confirmed as A. fumigatus (Aftr46-001) via ITS and β-tubulin sequencing, exhibited elevated minimum inhibitory concentrations (MICs) 16 µg/mL for itraconazole (ITC), 32 µg/mL for isavuconazole (ISA), 32 µg/mL for voriconazole (VRC), and 1 µg/mL for posaconazole (POS) by broth microdilution. E-test results revealed an ITR MIC of 12 µg/mL, ISA MIC 32 µg/mL, VRC MIC 32 µg/mL, and POS MIC of 2 µg/mL. The isolate exhibited MICs values at or above the CLSI and EUCAST epidemiological cutoff values (ECVs): 1 µg/mL for ITC, ISA, and VRC according to CLSI (with insufficient data to establish a POS ECV), and 1 µg/mL for ITC and VRC, 2 µg/mL for ISA, and 0.25 µg/mL POS per EUCAST criteria. Genotypic analysis identified a 46-nucleotide tandem repeat in the cyp51A promoter and two nonsynonymous mutations (Y46F, F70L). Discussion This represents the first report of a cyp51A TR46/Y46F/F70L-harboring A. fumigatus strain isolated from FK, with potential agricultural environmental origins, suggesting that this mutation may have become a potential driver of azole-resistant FK in areas with high agricultural exposure, urgently needing to be included in local treatment guidelines and active surveillance systems. The isolate’s resistance to all tested azoles underscores the clinical challenge posed by this genotype. Following this combined intervention, the patient's left eye vision improved from counting fingers at 1 m upon admission to a final visual acuity of 0.3, indicating that combined surgery and local high-dose drug delivery can serve as an effective strategy for drug-resistant FK. These findings highlight the importance of monitoring azole-resistant A. fumigatus strains to guide clinical treatment. The global increase in azole drug resistance further highlights the urgency and importance of rapid and accurate pathogen identification and drug resistance testing in the current environment.

研究领域: 医学微生物学 · 真菌学 · 抗微生物耐药性 · 眼科学 · 分子生物学 · 临床病理学
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Frontiers in Microbiology · 2024 · IF 4

Investigation of the fermentation filtrate from soapberry (Sapindus mukorossi Gaertn.) pericarp on improving the microbial diversity and composition of the human scalp

Xu Chong,Pan Danyang,Zhang Dexiang,Lin Lin,Chen Yiti,Liang Shuangcheng,He Jingyu

Introduction: Microorganisms as a component of scalp ecosystem play a vital role in human scalp health. Soapberry pericarp is employed in improving scalp health, and its content of active ingredients could be enhanced resulted in fermentation. This study aims to investigate the effect of the fermentation filtrate from soapberry pericarp on the diversity of scalp microorganisms.Methods: The components in fermentation filtrate from soapberry pericarp were analyzed by HPLC-Q-Orbitrap HRMS, and 16S and ITS sequences of 198 samples from three different used stages (Day 0, Day 7, Day 28) were sequenced using the Illumina Novaseq platform. Microbial diversity was assessed using alpha diversity (Chao1 and Shannon indexes) and beta diversity (weighted unifrac and unweighted unifrac). Principal coordinate analysis (PCoA) and linear discriminant analysis (LDA) effect size analysis (LEfSe) were used to visualize microbial variation among different stages.Results: There were 22 components were identified in the fermentation filtrate from soapberry pericarp by HPLC-Q-Orbitrap HRMS. The alpha-diversity and beta-diversity analyses showed that scalp microbial diversity and composition were influenced by the fermentation filtrate of soapberry pericarp. Based on functional analysis, this study found an enrichment of healthy scalp-related bacterial pathways, such as amino acid, nucleoside, and nucleotide biosynthesis, while a decrease in fungal pathogenesis pathways, specifically saprotroph and symbiotroph pathways, was observed.Discussion: The study described about the complex community dynamics of human scalp microorganisms during the stages of using the fermentation filtrate from soapberry pericarp. This result will help rationally utilize the fermentation filtrate from soapberry pericarp to keep or improve human scalp health.

研究领域: 微生物学 · 药学 · 生物技术 · 皮肤科
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Fermentation-Basel · 2025 ·Vol. 11 ·期 8 ·480 · IF 3.3

Decoding Forage-Driven Microbial–Metabolite Patterns: A Multi-Omics Comparison of Eight Tropical Silage Crops

Xianjun Lai,Siqi Liu,Yandan Zhang,Haiyan Wang,Lang Yan

Tropical forage crops vary widely in biochemical composition, resulting in inconsistent silage quality. Understanding how plant traits shape microbial and metabolic networks during ensiling is crucial for optimizing fermentation outcomes. Eight tropical forages—Sorghum bicolor(sweet sorghum),Sorghum×drummondii(sorghum–Sudangrass hybrid),Sorghum sudanense(Sudangrass),Pennisetum giganteum(giant Napier grass),Pennisetum purpureumcv. Purple (purple elephant grass),Pennisetum sinese(king grass),Leymus chinensis(sheep grass), andZea mexicana(Mexican teosinte)—were ensiled under uniform conditions. Fermentation quality, bacterial and fungal communities (16S rRNA and ITS sequencing), and metabolite profiles (untargeted liquid chromatography–mass spectrometry, LC-MS) were analyzed after 60 days. Sweet sorghum and giant Napier grass showed optimal fermentation, with high lactic acid levels (111.2 g/kg and 99.4 g/kg, respectively), low NH4+-N (2.4 g/kg and 3.1 g/kg), and dominantLactiplantibacillus plantarum. In contrast, sheep grass and Mexican teosinte exhibited poor fermentation, with high NH4+-N (6.7 and 6.1 g/kg) andClostridiumdominance. Fungal communities were dominated byKazachstania humilis(>95%), while spoilage-associated genera such asCladosporium,Fusarium, andTermitomycesproliferated in poorly fermented silages. Metabolomic analysis identified 15,827 features, with >3000 significantly differential metabolites between silages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed divergence in flavonoid biosynthesis, lipid metabolism, and amino acid pathways. In the sweet sorghum vs. sheep grass comparison, oxidative stress markers ((±) 9-HODE, Agrimonolide) were elevated in sheep grass, while sweet sorghum accumulated antioxidants like Vitamin D3. Giant Napier grass exhibited higher levels of antimicrobial flavonoids (e.g., Apigenin) than king grass, despite both being dominated by lactic acid bacteria. Sorghum–Sudangrass hybrid silage showed enrichment of lignan and flavonoid derivatives, while Mexican teosinte accumulated hormone-like compounds (Gibberellin A53, Pterostilbene), suggesting microbial dysbiosis. These findings indicate that silage fermentation outcomes are primarily driven by forage-intrinsic traits. A “forage–microbiota–metabolite” framework was proposed to explain how plant-specific properties regulate microbial assembly and metabolic output. These insights can guide forage selection and development of precision inoculant for high-quality tropical silage.

CAS / MDL: 103616-89-3
研究领域: 农学 · 微生物学 · 代谢组学 · 植物生物化学 · 发酵技术 · 生物信息学 · 环境微生物学
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