Comparative Phenotypic and Transcriptomic Analysis Reveals Distinct Yet Partially Convergent Mechanisms of Daphnetin and 6-Methylcoumarin Against Eucalyptus-Derived Ralstonia pseudosolanacearum

Discovery of penicillic acid from mangrove endophytic fungi: anti-Vibrio screening and cell envelope disruption in V. parahaemolyticus

Mangrove endophytic fungi are recognized as prolific sources of structurally diverse and bioactive natural products. In this study, 19 cultivable endophytic fungal strains were isolated and taxonomically characterized from mangrove plant tissues collected at the Shankou Mangrove Nature Reserve (Guangxi, China). One isolate, Aspergillus sclerotiorum BM19, exhibited broad-spectrum inhibitory activity against multiple aquatic pathogenic Vibrio strains. Bioactivity-guided fractionation of its ethyl acetate crude extract led to the isolation of penicillic acid (1), whose structure was fully elucidated by 1D/2D NMR and HRESIMS. Penicillic acid showed potent anti Vibrio parahaemolyticus activity with a minimum inhibitory concentration (MIC) of 6.25 μg/mL and displayed no obvious cytotoxicity toward human HaCaT keratinocytes. Growth curve assays revealed a concentration-dependent antibacterial effect: 0.5 × MIC delayed logarithmic growth, whereas 1 × and 2 × MIC completely suppressed bacterial proliferation. Transmission electron microscopy (TEM) visualized cellular distortion, compromised cell envelopes, and cytoplasmic leakage at MIC, with severe envelope disruption at 2 × MIC. Confocal laser scanning microscopy (CLSM) combined with SYTO 9/PI double staining further confirmed the concentration-dependent impairment of cell envelope integrity, as evidenced by reduced green fluorescence (intact cells) and increased red fluorescence (damaged cells). Collectively, these findings indicate that penicillic acid inhibits V. parahaemolyticus and is associated with concentration-dependent impairment of cell-envelope integrity. Although penicillic acid is a known mycotoxin, its selective activity against pathogenic vibrios and low toxicity to human keratinocytes highlight its potential as a lead compound for aquaculture applications. Nevertheless, further systematic evaluation of in vivo efficacy and biosafety is required prior to translational development.

Morpho-molecular approach reveals a myco-endophyte, Aspergillus novoparasiticus CBS126849 (MTCC-13997) from the roots of Capparis decidua with therapeutic and enzymatic potential

Comparative genomic analysis of two virulent Metarhizium rileyi (Hypocreales: Clavicipitaceae) isolates reveals enhanced virulence potential

Transcriptome and Metabolome Dissection of Multilayered Pydiflumetofen Resistance Mechanisms in Fusarium graminearum

This study systematically characterizes the resistance regulatory network of F. graminearum against pydiflumetofen, and provides theoretical guidance for the rational application and sustainable field resistance management of this fungicide.

Comparative transcriptome and proteome analysis of resistant and susceptible Talaromyces marneffei clinical isolates reveals a systemic multitiered defense network against azoles

ABSTRACT Talaromyces marneffei is a thermally dimorphic fungus causing life-threatening systemic mycosis in immunocompromised patients. The emergence of azole-resistant clinical isolates, especially those with reduced susceptibility to voriconazole (VOC) and fluconazole (FLC), presents a critical therapeutic challenge. Although target-gene alterations and efflux-related mechanisms have been reported in pathogenic fungi, the broader molecular basis distinguishing high-minimum-inhibitory concentration (MIC) and low-MIC T. marneffei clinical isolates remains incompletely defined. Here, we performed integrated transcriptomic (RNA-seq), proteomic (DIA-LC-MS/MS), and RT-qPCR analyses comparing four resistant and four susceptible T. marneffei clinical isolates. Differentially expressed genes and proteins were identified, functionally interpreted, and integrated to prioritize resistance-associated molecular candidates. The multi-omics results supported a constitutive, multitiered resistance-associated state involving transport and cell wall processes, redox-detoxification, mitochondrial metabolism, and stress regulatory adaptation. Signals involving coilin, CatA, and other discriminant features contributed to the multi-omics prioritization layer. RT-qPCR supported a 17-gene panel associated with transport, redox-detoxification, mitochondrial metabolism, and stress regulation. Five genes, PMAA_008970, PMAA_058960, PMAA_070510, PMAA_088690, and PMAA_092180, showed statistically significant R/S differences, while the remaining panel members were detectable and trend-supporting within the same functional framework. These findings refine a hierarchical azole-resistance model in T. marneffei and provide a focused candidate panel for future mechanistic validation.

Integrated Transcriptomic and Metabolomic Analyses Reveal Early Concentration-Dependent Responses of Astragalus membranaceus var. mongholicus Seedlings to Imidacloprid

Background: Imidacloprid, a widely used neonicotinoid insecticide, is routinely applied to control pests in Astragalus membranaceus var. mongholicus, a crucial medicinal herb producing Astragali Radix. However, the early short-term transcriptional and metabolic responses of its seedlings under imidacloprid gradient stress remain poorly characterized. Methods: In this study, 80-day seedlings were subjected to three foliar spray treatments: blank control (CK), the recommended imidacloprid concentration (2000-fold dilution, 475 mg·L−1), and an excessively high concentration (500-fold dilution, 1900 mg·L−1). Leaf samples were harvested 24 h post-treatment for untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) metabolomics (6 biological replicates) and RNA-seq transcriptome sequencing (3 biological replicates). Results: The low- and high-dose treatments induced 1076 and 860 differential metabolites and 6818 and 7283 differentially expressed genes, respectively. Flavonoids, saponins, terpenoids, amino acid metabolites, and energy-related pathways were prominently affected. KEGG enrichment indicated activation of flavone/flavonol biosynthesis, phenylpropanoid metabolism, amino acid metabolism, MAPK signaling, cutin/suberin/wax biosynthesis, and ABC transporter pathways, whereas high-dose exposure was associated with stronger changes in genes related to DNA replication and cell wall remodeling. Integrated network analysis highlighted CHS, PAL, MYC2, KCS, and ABCG40 as candidate regulators linking stress signaling, secondary metabolism, and metabolite transport. Conclusions: Seedlings of A. membranaceus var. mongholicus exhibit dose-dependent acute responses to imidacloprid. Moderate pesticide exposure primarily activates defensive secondary metabolism, whereas excessive dosage triggers genome-wide transcriptional reprogramming. This work identifies key metabolic pathways and hub genes, offering candidate molecular markers for investigating pesticide stress adaptation in medicinal Astragalus and guiding standardized pesticide application in cultivation.