Journal of microbiology and biotechnology最新文献

Lytic transglycosylases (LTs) are key enzymes involved in bacterial peptidoglycan remodeling. Here, we present the crystal structure of MltC from Acinetobacter baumannii (AbMltC), representing the second reported MltC structure after that of Escherichia coli (EcMltC). The AbMltC structure reveals a conserved catalytic residue, E224, equivalent to E217 of EcMltC, which directly participates in glycosidic bond cleavage. Notably, the substrate-binding residue R234, corresponding to R227 of EcMltC, is conserved in sequence but exhibits multiple conformations in AbMltC. This conformational heterogeneity suggests structural flexibility in substrate recognition and provides the structural insights consistent with prior hypothesis that R234 (R227 in EcMltC) functions as a molecular ratchet, facilitating processive cleavage.

The pathophysiology of major depressive disorder (MDD) remains incompletely understood, hindering the development of objective diagnostic markers. While the microbiota-gut-brain axis is implicated in MDD, the functional link between gut dysbiosis and systemic metabolism remains largely obscure. To address this, we employed an integrated multi-omics approach combining 16S rRNA gene sequencing, GC-MS analysis of urine and plasma, complemented by UPLC-QTOF-MS profiling of plasma, in a Korean cohort (n = 69). We identified distinct taxonomic shifts, specifically the enrichment of the Eubacterium eligens group and Veillonella in MDD patients. Integrated correlation analysis revealed a functional "gut-lipid axis", where these taxa were strongly associated with alterations in host acylcarnitine and fatty acid metabolism. Notably, diagnostic evaluation demonstrated that the plasma metabolic profile yielded superior predictive accuracy (AUC = 0.862) compared to the gut microbiota (AUC = 0.654). Our findings suggest that while the gut microbiome provides mechanistic insights into lipid dysregulation, the circulating metabolome serves as a more robust, proximal diagnostic readout for MDD.

This study was conducted to identify metabolic and gut microbial changes associated with the pathophysiology of irritable bowel syndrome (IBS) by comparing the plasma/urinary metabolite profiles and gut microbiota composition between healthy controls (HC) and IBS patients. There was no significant difference in overall microbial diversity; however, IBS patients showed relatively higher abundance of Christensenellaceae R-7 group, Clostridium sensu stricto 1, and Negativibacillus. Metabolite analysis identified statistically significant differences in 34 plasma metabolites (VIP > 1.2, q < 0.05). Metabolite set abundance analysis indicated that commonly disturbed metabolic pathways in both plasma and urinary metabolites were mainly related to carbohydrate, amino acid, and fatty acid metabolism. Among these metabolic pathways, fatty acid metabolism was associated with three metabolites that showed significant correlations with the discriminating gut microbial features, namely Clostridium sensu stricto 1, Negativibacillus, and Klebsiella. This study demonstrated that integrating the three datasets-plasma metabolites, urinary metabolites, and gut microbial communities-provides a comprehensive overview of IBS pathophysiology. Together, these findings indicate that functional interactions between discriminative gut microbial features and systemic metabolic alterations, particularly within fatty acid metabolism, may represent a mechanistic link between gut dysbiosis and the metabolic manifestations of IBS.

The skin serves as a vital barrier against environmental and biological stressors, and its impairment leads to premature aging and various dermatological disorders. The growing demand for natural, sustainable cosmetic ingredients has drawn attention to food industry byproducts as potential bioactive sources. Production of distilled soju generates substantial byproducts that are typically discarded but possess valuable metabolites. This study investigated the skin health-related functions of distilled soju byproducts fermented with the Saccharomyces cerevisiae MGE 3400 as a starter culture, which was isolated from a nuruk, compared with a commercial yeast. In vitro assays were performed to evaluate antioxidant activity and antimicrobial activity against the skin pathogens Candida albicans, Staphylococcus aureus, and Cutibacterium acnes, as well as moisturizing-related HAS2 expression, UV-protective effects, and wound-healing properties using the HaCaT cell line. S. cerevisiae MGE 3400 fermented distilled soju byproduct showed stronger antioxidant and antimicrobial activities than the control. In addition, they promoted the expression of hyaluronan synthase 2 (HAS2) and insulin-like growth factor 1 (IGF-1) genes, enhanced ultraviolet (UV) damage protection, and accelerated wound closure in keratinocyte HaCaT cells, suggesting an overall improvement in skin-regenerative potential. These findings suggest that S. cerevisiae MGE 3400 can enhance the functional properties of distilled soju byproduct, supporting their use as a sustainable source of natural ingredients for cosmetic and dermatological applications.

Ecological dysregulation leads to the progression of inflammatory bowel disease (IBD). The present study was designed to evaluate whether ginsenoside Rb3 (GR3) ameliorates dextran sulfate sodium (DSS)-induced colitis by modifying the microbiota. The results revealed that GR3 treatment with oral doses of 5 mg/kg suppressed DSS-induced colitis in mice, and its effects were evaluated using a combination of histological analysis, enzyme-linked immunosorbent assays (ELISA), and Western blotting. This was evidenced by a significant attenuation of symptoms such as weight loss, diarrhea, hematochezia, and colonic shortening in the DSS-induced colitis mice. Furthermore, GR3 treatment remarkably elevated the expression of tight junction proteins (occludin and zonula occludens-1) while reducing both inflammatory cell infiltration and inflammatory cytokine concentrations (TNF-α, IL-1β, IL-15, IL-17A, and IL-6). Intriguingly, GR3 treatment also mitigated DSS-induced intestinal dysbiosis by prominently increasing the proliferation of Lactobacillus and decreasing the relative abundance of Bacillus. Additionally, GR3 treatment significantly modified the metabolism of short-chain fatty acids in colitis mice, especially elevating the levels of acetic acid and butyric acid. These findings suggest that GR3 ameliorates colitis by reshaping the gut microbiota and improving the intestinal barrier and inflammation.

Recent studies highlight the immunomodulatory properties of Chaga mushrooms. Atopic dermatitis (AD) is a multifactorial skin disorder involving interactions between innate and adaptive immune responses. This investigation evaluates the anti-atopic dermatitis activity of a by-product from ethanol-extracted Chaga mushroom (E-CME), positioning it as a sustainable natural candidate for AD therapeutic development. The antioxidant potential of E-CME was assessed using DPPH radical scavenging, H₂O₂ scavenging, metal chelation, and FRAP assays. In vitro, its immunomodulatory effects were evaluated in HaCaT and RBL-2H3 cell lines by measuring cytokine release and β-Hexosaminidase activity. For in vivo analysis, E-CME was topically applied to BALB/c mice sensitized with Dermatophagoides farinae extract (DFE), with AD induced by DNCB. Post-treatment, inflammatory cytokine expression and MAPK marker expression were examined. E-CME treatment significantly improved dermatitis scores (p < 0.05), mast cell infiltration, serum immunoglobulin levels (24.07% increase of IgG2, 26.19% decrease of IgE), oxidative stress markers, and skin cytokine gene expression. Spleen and lymph node weights, plus splenocyte viability, also improved with E-CME treatment. These findings suggest that E-CME possesses substantial therapeutic potential for AD management, attributed to its antioxidant and immunomodulatory effects, possibly mediated by the inhibition of oxidative stress-associated inflammatory pathways.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, classified as a World Health Organization (WHO) grade IV astrocytoma. Despite multimodal therapies, the prognosis of patients with GBM remains poor, with a median survival of only 12-16 months. The highly invasive nature and therapeutic resistance of GBM underscore the need to identify novel molecular targets. Maternal embryonic leucine zipper kinase (MELK), a serine/threonine kinase of the Snf1/AMPK family, is highly expressed in GBM and regulates cell proliferation, cell cycle progression, and stemness; however, its downstream mechanisms are unclear. Nucleostemin (NS, GNL3) is a nucleolar GTP-binding protein involved in cell proliferation and p53 regulation; however, its regulation in GBM has not been fully elucidated. In this study, we identified NS as a novel MELK substrate in glioblastoma U87MG cells. MELK directly interacts with and phosphorylates NS, promoting its proteasomal degradation. MELK overexpression decreased NS expression, leading to enhanced p53 activation and G1 cell cycle arrest. Conversely, MELK knockdown restored NS stability and attenuated p53 activation. These findings define a previously unrecognized MELK-NS-p53 signaling axis that links kinase activity to the regulation of the cell cycle. Our fundings provide mechanistic insights into glioblastoma pathogenesis and suggest that targeting the MELK-NS pathway may be a potential therapeutic strategy for high-grade gliomas.

The present study was designed to evaluate the ameliorative effects of Rhodotorula mucilaginosa JAASSRY1 (JAASSRY1) on cyclophosphamide (CTX)-induced immunosuppression in mice. Immunocompromised mice were established by intraperitoneal injection of CTX (80 mg/kg/bw) for three consecutive days, followed by JAASSRY1 orally administered of JAASSRY1 for 21 days. Various immunological parameters, including immune organ indices, spleen cytokine levels, and immunoglobulin profiles, were evaluated. JAASSRY1 prevented CTX-induced immune damage by reversing weight loss and immune organ atrophy, suppressing the expression of IL-6, IL-17, and IFN-γ in the spleen (P< 0.01), and restoring levels of IgA and IgG, while up-regulating IL-4 (P< 0.01). Furthermore, JAASSRY1 attenuated immunosuppressive spleen injury by modulating the TLR4/MyD88/NF-κB pathway and regulating the Bax/Bcl-2 ratio. JAASSRY1 also alleviated CTX-induced dysbiosis by enhancing the abundance of Colidextribacter and reducing the levels of Parabacteroides and Bacteroides. A significant association was observed between specific gut microbiome Bacteroides and immune parameters (P< 0.01). Above all, JAASSRY1 demonstrates efficacy in ameliorating immunosuppression through the modulation of the "gut microbiota-spleen" axis, providing a basis for the development of probiotic formulations with immunomodulatory properties.

Cutibacterium acnes resistance to antibiotics poses a significant challenge in treating acne vulgaris. Bacteriophages offer a promising alternative to overcome this challenge given their specificity. In the current study, 15 bacteriophages were isolated from acne affected volunteers and subjected to whole genome sequencing to characterize their genetic features, diversity and endolysins encoding genes for further structural and functional analysis. Five representative endolysins (CAP 1-1, 6-3, 7-1, 10-3, and 12-3) were chosen for structural and functional analysis after average nucleotide identity (ANI) analysis where 5 different endolysins were categorized. Furthermore, molecular docking studies assessed the binding affinities of endolysins to common peptidoglycan fragments of C. acnes cell wall, identifying variations in the binding interactions as CAP 6-3, 7-1, and 12-3 had greater affinities for the NAG-NAM dimer, while CAP 1-1 and CAP 10-3 interacted preferentially with NAM-L-alanyl-D-isoglutamine (MDP). Residue-level interaction mapping revealed several conserved histidine residues; ASP170 is conserved in peptide-targeting endolysins. These results imply that C. acnes phage (CAP) endolysins may be functionally differentiated into peptide-targeting and glycan-targeting classes based on their substrate-binding preferences, in addition to the traditional classification of endolysins by bond-cleaving activity. Notably, by interfering with NOD2-mediated signaling, MDP binding may increase the potential for modifying host immunological responses. Together, this research offers novel molecular understandings of the substrate selectivity and possible immunomodulatory functions of CAP phage endolysins. These results provide computational insights into substrate specificity and potential immunomodulatory mechanisms of C. acnes phage endolysins therefore experimental validation is necessary to verify their biological and therapeutic significance.

Ulcerative colitis is chronic inflammatory bowel disease characterized by intestinal inflammation and barrier dysfunction. Probiotics and postbiotics have been proposed as dietary interventions for intestinal health; however, their comparative preventive effects remain unclear. In this study, we evaluated the preventive effects of probiotic and postbiotic forms of Lacticaseibacillus paracasei HY2782 in a dextran sulfate sodium (DSS)-induced colitis mouse model. Male C57BL/6 mice were orally administered live or heat-killed HY2782 prior to DSS exposure. Disease activity index, colon length, histopathological damage, inflammatory cytokine expression, and intestinal barrier-related gene expression were assessed, and gut microbiota composition was analyzed using 16S rRNA gene sequencing. Both probiotic and postbiotic forms of HY2782 significantly alleviated DSS-induced colitis, as evidenced by reduced disease activity, preserved colon length, improved histological features, and suppressed expression of pro-inflammatory cytokines. In addition, HY2782 treatment restored the expression of tight junction-related genes in colonic tissue. Gut microbiota analysis revealed limited but specific compositional changes following HY2782 administration, with no marked differences between live and heat-killed forms. These findings demonstrate that both probiotic and postbiotic forms of HY2782 exert preventive effects against DSS-induced colitis with no statistically significant differences between the two preparations. This suggests that HY2782 has significant potential as a versatile functional ingredient in both live and inactivated forms for the prevention of inflammatory bowel diseases, although further studies are needed to fully elucidate their distinct mechanistic roles.