Yerba Mate (YM) (Ilex paraguariensis) is a natural herbal supplement with a well-described anti-inflammatory capacity and beneficial effects in different inflammatory contexts such as insulin resistance or obesity. However, whether YM could improve other inflammatory conditions such as colitis or the immune cell population that can be modulated by this plant remains elusive. Here, by using 61 male and female C57BL/6/J wild-type (WT) mice and the dextran sodium sulfate (DSS)-induced acute colitis model, we evaluated the effect of YM on colitis symptoms and macrophage polarization. Our results showed that the oral administration of YM reduces colitis symptoms and improves animal survival. Increasing infiltration of anti-inflammatory M2 macrophage was observed in the colon of the mice treated with YM. Accordingly, YM promoted M2 macrophage differentiation in vivo. However, the direct administration of YM to bone marrow-derived macrophages did not increase anti-inflammatory polarization, suggesting that YM, through an indirect mechanism, is able to skew the M1/M2 ratio. Moreover, YM consumption reduced the Eubacterium rectale/Clostridium coccoides and Enterobacteriaceae groups and increased the Lactobacillus/Lactococcus group in the gut microbiota. In summary, we show that YM promotes an immunosuppressive environment by enhancing anti-inflammatory M2 macrophage differentiation, reducing colitis symptoms, and suggesting that YM consumption may be a good cost-effective treatment for ulcerative colitis.

The growing threat of antimicrobial resistance has intensified the search for new bioactive compounds, particularly in extreme environments such as Antarctica. Streptomyces fildesensis So13.3, isolated from Antarctic soil, harbours a biosynthetic gene cluster (BGC) associated with actinomycin D production, an antibiotic with biomedical relevance. This study investigates the regulatory role of TetR/AcrR transcription factors encoded within this biosynthetic gene cluster (BGC), focusing on their structural features and expression under different nutritional conditions. Additionally, we propose that repressing an active pathway could lead to the activation of silent biosynthetic routes, and our in-silico analysis provides a foundation for selecting key mutations and experimentally validating this strategy. Expression analysis revealed that TetR-279, in particular, was upregulated in ISP4 and IMA media, suggesting its participation in nutrient-dependent BGC regulation. Structural modelling identified key differences between TetR-206 and TetR-279, with the latter containing a tetracycline-repressor-like domain. Molecular dynamics simulations confirmed TetR-279’s structural stability but showed that the S166P CRISPy-web-guided mutation considerably affected its flexibility, while V167A and V167I had modest effects. These results underscore the importance of integrating omics, structural prediction, and gene editing to evaluate and manipulate transcriptional regulation in non-model bacteria. Targeted disruption of TetR-279 may derepress actinomycin biosynthesis, enabling access to silent or cryptic secondary metabolites with potential pharmaceutical applications.

The growing threat of antimicrobial resistance has driven the search for new bioactive compounds in extreme environments such as Antarctica. Streptomyces fildesensis So13.3, isolated from Antarctic soil, has been shown to contain a biosynthetic gene cluster associated with producing actinomycin D, an antibiotic with therapeutic potential. In this study, we analysed the regulatory role of TetR/AcrR family transcription factors present within this BGC, focusing on their activation under different nutritional conditions and their structural scharacterisation using bioinformatics tools and molecular dynamics simulations. The results showed that TetR/AcrR expression increased significantly in ISP4 and IMA media, suggesting their involvement in nutrient-dependent regulation of the cluster. At the structural level, two TetR proteins (TetR-206 and TetR-279) were modelled, with the latter standing out due to a C-terminal tetracycline repressor-like domain. A 200 ns molecular dynamics simulation was performed in GROMACS to evaluate the stability and flexibility of TetR-279, including analysis of point mutations (S166P, V167A, V167I). The S166P mutation significantly impacted structural flexibility, while V167A and V167I caused only minor alterations. This work demonstrates the value of integrating omics approaches, structural modelling, and gene editing with CRISPR to study and potentially activate silent BGCs in non-model bacteria such as Antarctic Streptomyces. In particular, the targeted inhibition of TetR-279 may trigger metabolic rewiring and facilitate the expression of novel antibiotics encoded in cryptic biosynthetic gene clusters.

This study presents the first annotated genome of the Antarctic fungus Pseudogymnoascus australis UA-032-E, revealing significant biosynthetic potential with 44 predicted biosynthetic gene clusters (BGCs) identified through antiSMASH analysis. These BGCs include nonribosomal peptide synthetases (NRPS), type I polyketide synthases (PKS), and hybrid systems, indicating a diverse capacity for secondary metabolite production. BiG-SCAPE analysis grouped these clusters into 41 gene cluster families, with most being singletons, demonstrating low genetic redundancy and high structural diversity. To activate silent pathways, we employed elicitors (NPS and LPS) across multiple culture media, successfully inducing previously undetected metabolic activity. Using an integrated LC–QTOF–MS/MS approach combined with the GNPS and SIRIUS platforms, a total of 75 features were detected, including cyclodipeptides [cyclo-(Pro-Val), cyclo-(Leu-Leu)], maculosin, and betaine lipids such as DGTS 18:2—compounds linked to stress adaptation and biological activities in the literature. The YES medium supplemented with LPS elicitation yielded the highest metabolic diversity, suggesting this combination effectively stimulates specialized metabolism. Our findings demonstrate the value of combining genomic and metabolomic approaches to unlock the chemical potential of psychrophilic fungi. The genomic resource presented here provides a foundation for future functional studies and targeted bioprospecting of this Antarctic fungus for novel metabolites with potential biotechnological applications.

Understanding the molecular intricacies of Pediocin PA-1 interactions with biological membranes reveals a distinctive mechanism with promising implications beyond its effects on prokaryotic membranes. To elucidate the behavior of this bacteriocin, molecular dynamics simulations were performed under both NVT and NPT ensembles, as well as with NγT to accelerate biological processes by applying different surface tensions. The alpha-helix region plays a pivotal role, maintaining a stable orientation perpendicular to the membrane, optimizing interactions and minimizing hydrogen bond resistance. The subsequent poration mechanism, essential for the bacteriocin's cytotoxic potential, involves lipid displacement facilitated by the insertion of the alpha-helix. Notably, the restricted movement of the C-terminal region, stabilized by a disulfide bridge, ensures precise spatial arrangements, enhancing the peptide's effective insertion and poration. Molecular dynamics simulations highlight Pediocin PA-1's impact on membrane properties, including thickness, lipid area, and lateral diffusion. The bacteriocin's hydrophobicity and the selective orientation of its N-terminal region contribute significantly to membrane destabilization, providing key insights into its molecular behavior. Beyond its structural characteristics, Pediocin PA-1 exhibits notable cytotoxic potential against colon cancer cells. Its membrane-disruptive effects, coupled with selective activity towards cancerous cells, position the bacteriocin as a promising candidate for targeted cancer therapy. This study explores the interplay between temperature and surface tension, further advancing our understanding of Pediocin PA-1's versatile behavior. As research progresses, the complex interaction between this bacteriocin and biological membranes not only deepens our understanding of its mechanism but also opens new avenues for potential therapeutic applications.

Ovarian cancer (OC) remains one of the deadliest gynecological malignancies, largely due to late diagnosis and the emergence of resistance to platinum–based chemotherapy. Long non–coding RNAs (lncRNAs) have recently emerged as key regulators of tumor progression and therapeutic adaptation. In this study, we performed integrative transcriptomic profiling of patient–derived TCGA ovarian tumor samples and carboplatin–resistant A2780 (CBDCA–R–A2780) cells to identify lncRNAs whose dysregulation overlaps between a cell–line resistance model and patient tumors. Our analyses revealed extensive transcriptional remodeling across both datasets, with MNX1–AS1 consistently emerging as a strongly deregulated transcript. Differential expression analysis showed robust upregulation of MNX1–AS1 in resistant cells and tumor tissues, accompanied by correlations with epithelial–mesenchymal transition (EMT)–related transcription factors such as FOXA1 and SNAI2 and inverse associations with epithelial markers including CDH1. Computational predictions using RIblast identified specific MNX1–AS1 binding regions with candidate miRNAs and mRNAs, prioritizing EMT–related transcripts (e.g., SNAI2, FOXA1, ZEB1) with favorable hybridization energies for future validation. Additional prioritized interactors included genes linked to stress response (IER2, FOSB) and invasion (MMP11, MMP1). Because A2780 has been discussed as an endometrioid–like/non–serous ovarian cancer model, mechanistic inferences primarily apply to this in vitro context, while TCGA analyses provide associative support rather than mechanistic validation. Collectively, these findings highlight MNX1–AS1 as a candidate regulator associated with transcriptional reprogramming in OC and a promising prognostic biomarker warranting further functional testing.