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Background/Objectives: Actinobacteria are one of the largest bacterial phyla. These microbes produce bioactive compounds, such as antifungals, antibiotics, immunological modulators, and anti-tumor agents. Studies on actinobacteria isolated from the Brazilian Savannah biome (Cerrado) are scarce and mostly address metagenomics or the search for hydrolytic enzyme-producing microbes. Solanum lycocarpum (lobeira) is a tree widely employed in regional gastronomy and pharmacopeia in Central Brazil. Methods: In this work, 60 actinobacteria isolates were purified from the rhizosphere of S. lycocarpum. Eight Streptomyces spp. isolates were selected for in vitro antifungal activity against Cryptococcus neoformans H99, the C. neoformans 89-610 fluconazole-tolerant strain, C. gattii NIH198, Candida albicans, C. glabrata, and C. parapsilosis. The ability of the aqueous extracts of the isolates to induce the in vitro secretion of tumor necrosis factor (TNF-α), nitric oxide (NO), interleukin-6 (IL-6), and IL-10 by murine macrophages was also evaluated. Results: All extracts showed antifungal activity against at least two yeast species. Streptomyces spp. LAP11, LDB2, and LDB17 inhibited C. neoformans growth by 40–93%. Most extracts (except LAP2) also inhibited C. gattii. None inhibited C. albicans, but all inhibited C. glabrata (40–90%). Streptomyces sp. LAP8 extract increased nitric oxide production by approximately 347-fold in murine macrophages, while LDB11 extract suppressed LPS-induced TNF-α production by 70% and simultaneously increased IL-10 secretion, suggesting immunosuppressive potential. Conclusions: The results revealed that Cerrado actinobacteria-derived aqueous extracts are potential sources of antifungal and immunomodulatory biocompounds. Full article

Background: Antibacterial resistance (ABR) poses a major challenge to global health, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the prominent multidrug-resistant strains. MRSA has developed resistance through the expression of Penicillin-Binding Protein 2a (PBP2a), a key transpeptidase enzyme involved in bacterial cell wall biosynthesis. Objectives: The objective was to design and characterize a novel small-molecule inhibitor targeting PBP2a as a strategy to combat MRSA. Methods: We synthesized a new indole triazole conjugate (ITC) using eco-friendly and click chemistry approaches. In vitro antibacterial tests were performed against a panel of strains to evaluate the ITC antibacterial potential. Further, a series of in silico evaluations like molecular docking, MD simulations, free energy landscape (FEL), and principal component analysis (PCA) using the crystal structure of PBP2a (PDB ID: 4CJN), in order to predict the mechanism of action, binding mode, structural stability, and energetic profile of the 4CJN-ITC complex. Results: The compound ITC exhibited noteworthy antibacterial activity, which effectively inhibited the selected strains. Binding score and energy calculations demonstrated high affinity of ITC for the allosteric site of PBP2a and significant interactions responsible for complex stability during MD simulations. Further, FEL and PCA provided insights into the conformational behavior of ITC. These results gave the structural clues for the inhibitory action of ITC on the PBP2a. Conclusions: The integrated in vitro and in silico studies corroborate the potential of ITC as a promising developmental lead targeting PBP2a in MRSA. This study demonstrates the potential usage of rational drug design approaches in addressing therapeutic needs related to ABR. Full article

Silicon has a striking similarity to carbon and is found in plant cells. However, there is no specific role that has been assigned to silicon in the life cycle of plants. The amount of silicon in plant cells is species specific and can reach levels comparable to macronutrients. Silicon is used extensively in artificial intelligence, nanotechnology, and the digital revolution, and thus can serve as an informational molecule such as nucleic acids. The diverse potential of silicon to bond with different chemical species is analogous to carbon; thus, it can serve as a structural candidate similar to proteins. The discovery of large amounts of silicon on Mars and the moon, along with the recent development of enzyme that can incorporate silicon into organic molecules, has propelled the theory of creating silicon-based life. The bacterial cytochrome has been modified through directed evolution such that it could cleave silicon–carbon bonds in organo-silicon compounds. This consolidates the idea of utilizing silicon in biomolecules. In this article, the potential of silicon-based life forms has been hypothesized, along with the reasoning that autotrophic virus-like particles could be used to investigate such potential. Such investigations in the field of synthetic biology and astrobiology will have corollary benefits for Earth in the areas of medicine, sustainable agriculture, and environmental sustainability. Full article

Leather biodegradation is a complex microbial process with increasing relevance for sustainable waste management. In this study, we investigated bacterial communities responsible for the degradation of leather treated with different tanning agents (chrome, Zeolite, Biole^®) using high-throughput 16S rRNA gene sequencing and metatranscriptomic analysis. Proteobacteria, Bacteroidetes, and Patescibacteria emerged as the dominant phyla, while genera such as Acinetobacter, Pseudomonas, and Sphingopyxis were identified as key contributors to enzymatic activity and potential metal resistance. A total of 1302 enzymes were expressed across all the conditions, including 46 proteases, with endopeptidase La, endopeptidase Clp, and methionyl aminopeptidase being the most abundant. Collagen samples exhibited the highest functional diversity and total enzyme expression, whereas chrome-treated samples showed elevated protease activity, indicating selective pressure from heavy metals. Differential enzyme expression patterns were linked to both the microbial identity and tanning chemistry, revealing genus- and treatment-specific enzymatic signatures. These findings deepen our understanding of how tanning agents modulate the microbial structure and function and identify proteases with potential applications in the bioremediation and eco-innovation of leather waste processing. Full article

Soil salinization poses a significant constraint to agricultural productivity. However, certain plant growth-promoting bacteria (PGPB) can mitigate salinity stress and enhance crop performance. In this study, a bacterial isolate, R-18, isolated from saline-alkali soil in Ningxia, China, was identified as Enterobacter bugandensis based on 16S rRNA gene sequencing. The isolate was characterized for its morphological, biochemical, and plant growth-promoting traits and was evaluated for its potential to alleviate NaCl-induced stress in maize (Zea mays L.) under hydroponic conditions. Isolate R-18 exhibited halotolerance, surviving at NaCl concentrations ranging from 2.0% to 10.0%, and alkaliphilic adaptation, growing at pH 8.0–11.0. Biochemical assays confirmed it as a Gram-negative bacterium, displaying positive reactions in the Voges–Proskauer (V–P) tests, catalase activity, citrate utilization, fluorescent pigment production, starch hydrolysis, gelatin liquefaction, and ammonia production, while testing negative for the methyl red and cellulose hydrolysis. Notably, isolate R-18 demonstrated multiple plant growth-promoting attributes, including nitrogen fixation, phosphate and potassium solubilization, ACC deaminase activity, and indole-3-acetic acid (IAA) biosynthesis. Under 100 mM NaCl stress, inoculation with isolate R-18 significantly enhanced maize growth, increasing plant height, stem dry weight, root fresh weight, and root dry weight by 20.64%, 47.06%, 34.52%, and 31.25%, respectively. Furthermore, isolate R-18 improved ion homeostasis by elevating the K⁺/Na⁺ ratio in maize tissues. Physiological analyses revealed increased chlorophyll and proline content, alongside reduced malondialdehyde (MDA) levels, indicating mitigated oxidative damage. Antioxidant enzyme activity was modulated, with decreased superoxide dismutase (SOD) and peroxidase (POD) activities but increased catalase (CAT) activity. These findings demonstrated that Enterobacter bugandensis R-18 effectively alleviated NaCl-induced growth inhibition in maize by enhancing osmotic adjustment, reducing oxidative stress, and improving ion balance. Full article

Soil salinity adversely affects crop growth and development, leading to reduced soil fertility and agricultural productivity. The indigenous salt-tolerant plant growth-promoting rhizobacteria (PGPR), as a sustainable microbial resource, do not only promote growth and alleviate salt stress, but also improve the soil microecology of crops. The strain H5 isolated from saline-alkali soil in Bachu of Xinjiang was studied through whole-genome analysis, functional annotation, and plant growth-promoting, salt-tolerant trait gene analysis. Phylogenetic tree analysis and 16S rDNA sequencing confirmed its classification within the genus Halomonas. Functional annotation revealed that the H5 genome harbored multiple functional gene clusters associated with plant growth promotion and salt tolerance, which were critically involved in key biological processes such as bacterial survival, nutrient acquisition, environmental adaptation, and plant growth promotion. The pot experiment under moderate salt stress demonstrated that seed inoculation with Halomonas sp. H5 not only significantly improved the agronomic traits of tomato seedlings, but also increased plant antioxidant enzyme activities under salt stress. Additionally, soil analysis revealed H5 treatment significantly decreased the total salt (9.33%) and electrical conductivity (8.09%), while significantly improving organic matter content (11.19%) and total nitrogen content (10.81%), respectively (p < 0.05). Inoculation of strain H5 induced taxonomic and functional shifts in the rhizosphere microbial community, increasing the relative abundance of microorganisms associated with plant growth-promoting and carbon and nitrogen cycles, and reduced the relative abundance of the genera Alternaria (15.14%) and Fusarium (9.76%), which are closely related to tomato diseases (p < 0.05). Overall, this strain exhibits significant potential in alleviating abiotic stress, enhancing growth, improving disease resistance, and optimizing soil microecological conditions in tomato plants. These results provide a valuable microbial resource for saline soil remediation and utilization. Full article

The rise of multidrug-resistant Pseudomonas aeruginosa underscores the need for novel therapeutic targets beyond conventional peptidoglycan biosynthesis. Some bacterial strains bypass MurA inhibition by fosfomycin via a cell wall salvage pathway. This study targeted P. aeruginosa AmgK (PaAmgK) and MurU (PaMurU) to identify inhibitors that could complement fosfomycin therapy. A malachite-green-based dual-enzyme assay enabled efficient activity measurements and high-throughput chemical screening. Screening 232 compounds identified Congo red and CTAB as potent PaMurU inhibitors. A targeted mass spectrometric analysis confirmed the selective inhibition of PaMurU relative to that of PaAmgK. Molecular docking simulations indicate that Congo red preferentially interacts with PaMurU through electrostatic contacts, primarily involving the residues Arg28 and Arg202. The binding of Congo red to PaMurU was corroborated further using SUPR-differential scanning fluorimetry (SUPR-DSF), which revealed ligand-induced thermal destabilization. Ongoing X-ray crystallographic studies, in conjunction with site-directed mutagenesis and enzyme kinetic analyses, aim to elucidate the binding mode at an atomic resolution. Full article

Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article

Cellulose, the most abundant organic polymer in soil, is degraded by the action of microbial communities. Cellulolytic taxa are widespread in soils, enhancing the biodegradation of cellulose by the synergistic action of different cellulase enzymes. β-glucosidases are the last enzymes responsible for the degradation of cellulose by producing glucose from the conversion of the disaccharide cellobiose. Different soils from the states of Delaware, Maryland, New Jersey, and New York were analyzed by direct DNA extraction, PCR analysis, and next generation sequencing of amplicon sequences coding for β-glucosidase genes. To determine the community structure and diversity of microorganisms carrying β-glucosidase genes, amplicon sequence variant analysis was performed. Results showed that the majority of β-glucosidase genes did not match any known phylum or genera with an average of 84% of sequences identified as unclassified. The forest soil sample from New York showed the highest value with 95.62%. When identification was possible, the bacterial phyla Pseudomonadota, Actinomycetota, and Chloroflexota were found to be dominant microorganisms with β-glucosidase genes in soils. The Delaware soil showed the highest diversity with phyla and genera showing the presence of β-glucosidase gene sequences in bacteria, fungi, and plants. However, the Chloroflexota genus Kallotanue was detected in 3 out of the 4 soil locations. When phylogenetic analysis of unclassified β-glucosidase genes was completed, most sequences aligned with the Chloroflexota genus Kallotenue and the Pseudomonadota species Sphingomonas paucimobilis. Since most sequences did not match known phyla, there is tremendous potential to discover new enzymes for possible biotechnological and pharmaceutical applications. Full article

Myocardial infarction (MI) is an inflammatory disease responsible for approximately 75% of sudden cardiac deaths. In this study, we aimed to evaluate the cardio-protective influence of microencapsulated probiotic and synbiotic dietary supplements in vivo and in molecular docking studies. MI was induced in rats with the injection of isoproterenol (i.p. 67 mg/kg). Plasma lipid profiles and the levels of oxidative stress markers, inflammatory markers, and cardiac enzymes were determined. The expression levels of MMP-7 and IL-1β in the heart muscle were measured. The impact of dietary supplements on fecal bacterial counts was evaluated across all rat groups. A histopathological examination of cardiac tissue was performed. The cardio-protective potential of cyanidin 3-diglucoside 5-glucoside and arabinoxylan was studied using molecular docking. The results demonstrate that all tested dietary supplements induced an improvement in all the biochemical parameters in association with an improvement in myocardial muscle tissue. The mRNA expression levels of MMP-7 and IL-1β were significantly downregulated by all dietary supplements. All dietary supplements increased the fecal counts of probiotic strains. In the molecular docking analysis, cyanidin 3-diglucoside 5-glucoside exhibited binding affinity values of −8.8 and −10 for lactate dehydrogenase (LDH) and Paraoxonase 1 (PON1), respectively. Arabinoxylan showed similar binding affinity (−8.8) for both LDH and PON1. Conclusion: Microencapsulated probiotic and synbiotic dietary supplements demonstrated notable cardio-protective influence in vivo and in molecular docking studies. These supplements may serve as promising candidates for the prevention of myocardial infarction. Full article

Stipagrostis pennata is an important plant in desert ecosystems. Its seed-endophytic bacteria may play a critical role in plant growth and environmental adaptation processes. This study systematically analyzed the community composition and potential plant growth-promoting (PGP) functions of seed-endophytic bacteria associated with S. pennata. The results showed that while the overall diversity of bacterial communities from different sampling sites was similar, significant differences were observed in specific functional genes and species abundances. Nine endophytic bacterial strains were isolated from the seeds, among which Bacillus altitudinis strain L7 exhibited phosphorus solubilizing capabilities, nitrogen fixing, IAA production, siderophore generation, and multi-hydrolytic enzyme activities. Additionally, the genomic sequencing of L7 revealed the key genes involved in plant growth promotion and environmental adaptation, including Na⁺ efflux systems, K⁺ transport systems, compatible solute synthesis genes, and the gene clusters associated with nitrogen metabolism, IAA synthesis, phosphate solubilization, and siderophore synthesis. Strain L7 exhibits salt and osmotic stress tolerance while promoting plant growth, providing a promising candidate for desert microbial resource utilization and plant biostimulant development. Full article

Ecological restoration in the cold and high-altitude mining areas of the Qinghai–Tibet Plateau is faced with dual challenges of extreme environments and insufficient microbial adaptability. This study aimed to screen local microbial resources with both extreme environmental adaptability and plant-growth-promoting functions. Local fungi (DK; F18-3) and commercially available bacteria (B0) were used as materials to explore their regulatory mechanisms for plant growth, soil physicochemical factors, microbial communities, and metabolic profiles in the field. Compared to bacterial treatments, local fungi treatments exhibited stronger ecological restoration efficacy. In addition, the DK and F18-3 strains, respectively, increased shoot and root biomass by 23.43% and 195.58% and significantly enhanced soil nutrient content and enzyme activity. Microbiome analysis further implied that, compared with the CK, DK treatment could significantly improve the α-diversity of fungi in the rhizosphere soil (the Shannon index increased by 14.27%) and increased the amount of unique bacterial genera in the rhizosphere soil of plants, totaling fourteen genera. Meanwhile, this aggregated the most biomarkers and beneficial microorganisms and strengthened the interactions among beneficial microorganisms. After DK treatment, twenty of the positively accumulated differential metabolites (DMs) in the plant rhizosphere were highly positively associated with six plant traits such as shoot length and root length, as well as beneficial microorganisms (e.g., Apodus and Pseudogymnoascus), but two DMs were highly negatively related to plant pathogenic fungi (including Cistella and Alternaria). Specifically, DK mainly inhibited the growth of pathogenic fungi through regulating the accumulation of D-(+)-Malic acid and Gamma-Aminobutyric acid (Cistella and Alternaria decreased by 84.20% and 58.53%, respectively). In contrast, the F18-3 strain mainly exerted its antibacterial effect by enriching Acidovorax genus microorganisms. This study verified the core role of local fungi in the restoration of mining areas in the Qinghai–Tibet Plateau and provided a new direction for the development of microbial agents for ecological restoration in the Qinghai–Tibet Plateau. Full article

This study investigated the effects of reduced nitrogen combined with an organic fertilizer on maize yield, soil microbial communities, and enzyme activities to optimize fertilization strategies. A field experiment on cinnamon soil in Yuncheng, Shanxi, was conducted and included six treatments: no fertilizer (CK), conventional N (NC0, 180 kg N/ha), sole organic fertilizer (CN0, 3000 kg/ha), and reduced-N + organic fertilizer (CN1: 90 kg N/ha + 3000 kg/ha; CN2: 135 kg N/ha + 3000 kg/ha; and CN3: 180 kg N/ha + 3000 kg/ha). We analyzed yield components, soil nutrients, urease and invertase activities, and bacterial community structure (16S rRNA sequencing). The key results are as follows: CN1 achieved the highest yield (9764.87 kg/ha), which was 46.8% higher than CK. CN2 maintained comparable yields while delivering higher enzyme activities and microbial abundance, positioning this strategy as suitable for soil remediation. Co-application enriched two beneficial phyla, Proteobacteria and Planctomycetota (19% in CN2), with Proteobacteria positively correlating with urease activity and alkali-hydrolyzable N (p < 0.05), while Verrucomicrobiota negatively correlated with urease activity. In conclusion, 25–50% N reduction with an organic fertilizer (3000 kg/ha) synergistically enhances yield, soil enzymes, and beneficial microbiota, supporting sustainable high-yield agriculture with improved soil fertility. Full article

Background: Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. Here, we report the construction and characterization of self-assembling 60-subunit icosahedral nanoparticle SARS-CoV-2 vaccines using the bacterial enzyme lumazine synthase (LuS). Methods and Results: Nanoparticles displaying prefusion-stabilized SARS-CoV-2 spike ectodomains fused to the surface-exposed amino terminus of LuS were designed using structure-guided approaches. Negative stain-electron microscopy studies of purified nanoparticles were consistent with self assembly into 60-mer nanoparticles displaying 20 spike trimers. After two intramuscular doses, these purified spike-LuS nanoparticles elicited significantly higher SARS-CoV-2 neutralizing activity than spike trimers in vaccinated mice. Furthermore, intramuscular DNA priming and intranasal boosting with a SARS-CoV-2 LuS nanoparticle vaccine stimulated mucosal IgA responses. Conclusion: These data identify LuS nanoparticles as highly immunogenic SARS-CoV-2 vaccine candidates and support the further development of this platform against SARS-CoV-2 and its emerging variants. Full article

Aromatic compounds are vital in both natural and synthetic chemistry, and they are traditionally sourced from non-renewable petrochemicals. However, plant biomass, particularly lignin, offers a renewable alternative source of aromatic compounds. Lignin, a complex polymer found in plant cell walls, is the largest renewable source of aromatic compounds, though its degradation remains challenging. Lignin can be chemically degraded through oxidation, acid hydrolysis or solvolysis. As an alternative, microorganisms, including fungi, could offer a sustainable alternative for breaking down lignin. The aromatic compounds released from lignin, by either microbial, chemical or enzymatic degradation, can be used by microorganisms to produce valuable compounds. Fungi possess unique enzymes capable of converting aromatic compounds derived from lignin or other sources into chemical building blocks that can be used in several industries. However, their aromatic metabolic pathways are poorly studied compared to bacterial systems. In the past, only a handful of genes and enzymes involved in the aromatic metabolic pathways had been identified. Recent advances in genomics, proteomics, and metabolic engineering are helping to reveal these metabolic pathways and identify the involved genes. This review highlights recent progress in understanding fungal aromatic metabolism, focusing on how Aspergillus niger converts plant-derived aromatic compounds into potentially useful products and the versatility of aromatic metabolism within the Aspergillus genus. Addressing the current knowledge gaps in terms of fungal pathways could unlock their potential for use in sustainable technologies, promoting eco-friendly production of chemical building blocks from renewable resources or bioremediation. Full article