Search Results (384)

Antimicrobial resistance (AMR) has emerged as a global health crisis, with methicillin-resistant Staphylococcus aureus (MRSA) representing one of the most clinically significant multidrug-resistant pathogens. In this study, three structurally unique anthracycline derivatives—keto-ester (1), 4-deoxy-ε-pyrromycinone (2), and misamycin (3)—were first isolated and characterized from the fermentation broth of the marine-derived Streptomyces tauricus NBUD24. These compounds exhibited notable antibacterial efficacy against MRSA, with minimum inhibitory concentrations (MICs) ranging from 16 to 32 µg/mL. Cytotoxicity assays confirmed their safety profile at therapeutic concentrations. The biofilm formation assay demonstrated that 4-deoxy-ε-pyrromycinone inhibited biofilm formation of MRSA ATCC43300, with an inhibition rate of 64.4%. Investigations of antibacterial mechanisms revealed that these compounds exert antibacterial effects primarily through disruption of bacterial cell wall integrity and destruction of DNA structure. These findings underscore the potential of marine-derived microbial metabolites as promising scaffolds for developing next-generation antimicrobial candidates to combat drug-resistant infections. Full article

This study investigates the potential for the microbial transformation of camelliagenin B, a saponin derived from Camellia oleifera seed cake meal, to develop novel metabolites. We employed three microbial strains, specifically Bacillus subtilis ATCC 6633, Bacillus megaterium CGMCC 1.1741, and Streptomyces griseus ATCC 13273, to biotransform camelliagenin B into its derivatives. The compounds were purified and separated using chromatographic techniques, such as high-performance liquid chromatography (HPLC). Structural identification was carried out using spectroscopic methods, including nuclear magnetic resonance (NMR) and mass spectrometry (MS). Ten bioactive compounds were obtained (1a-1j), of which nine were novel with multiple tailoring reactions, such as allyl oxidation, C-C double-bond rearrangement, hydroxylation, dehydrogenation, and glycosylation, observed in camelliagenin B analogs. The structures of these compounds were determined by 1D/2D NMR and HR-ESI-MS analysis. Therefore, this study showcases the capacity of microbial transformation as a sustainable and environmentally friendly method for generating bioactive compounds from C. oleifera seed cake meals. The individual chemicals can potentially facilitate the design of novel medicinal agents, functional foods, and natural preservatives. Full article

The ongoing threat of antimicrobial-resistant pathogens has intensified the need for new antimicrobial agents, making the discovery of novel natural products crucial. This study focuses on the isolation and characterization of a novel Streptomyces species from the Anjar region in Lebanon, an area rich in microbial diversity that is largely unexplored for its biotechnological potential. Soil samples were collected and processed, leading to the isolation of Streptomyces strain ANJ10. Comprehensive morphological, physiological, and genomic analyses were conducted, including whole-genome sequencing (WGS) to identify biosynthetic gene clusters (BGCs) and broth microdilution (BMD) assays to evaluate antimicrobial activity. The ANJ10 genome revealed 42 BGCs, significantly more than the average number in Streptomyces species, suggesting a high potential for secondary metabolite production. Phylogenetic analysis confirmed ANJ10 as a novel species, and BMD assays demonstrated its strong antimicrobial activity against several gram-negative pathogens, specifically, Acinetobacter baumannii. These findings underscore the potential of this strain as a significant source of new antimicrobial compounds, reinforcing the importance of exploring underexploited environments like Lebanon for microbial bioprospecting. Full article

Microorganisms take an active part in the processes of microbiologically influenced corrosion, which is protected against by using bactericides—often toxic compounds—with inhibitory properties. There are many studies of eco-friendly “green” biocides/inhibitors, in particular those based on microbial metabolites. Indicators for the processes of microbial corrosion of steel 3 induced by the sulfate-reducing bacteria Desulfovibrio oryzae NUChC SRB2 under the influence of the strains Bacillus velezensis NUChC C2b and Streptomyces gardneri ChNPU F3 have not been investigated, which was the aim of this study. The agar well diffusion method (to determine the antibacterial properties of the supernatants) was used, along with the crystal violet (to determine the biomass of the biofilm on the steel) and gravimetric methods (to determine the corrosion rate). A moderate adhesiveness to steel 3 was established for D. oryzae due to its biofilm-forming ability. The presence of a supernatant on cultures of S. gardneri, B. velezensis and their mixture (2:1) did not reduce the biofilm-forming properties of D. oryzae. Compared to the control, a decrease in the corrosion rate was recorded for the variant of the mixture of the studied bacterial culture supernatants. This indicates the potential of this mixture for use in corrosion protection in environments with sulfate-reducing bacteria, which requires further research. Full article

Chagas disease (ChD) caused by Trypanosoma cruzi remains a major public health concern, affecting approximately 8 million people worldwide. However, the number of undiagnosed cases is likely much higher. Existing treatments rely on benznidazole and nifurtimox which, despite their efficacy during the acute phase of infection, are often associated with severe side effects that can be life-threatening. As a promising alternative, actinomycetes—which are renowned for producing pharmacologically and industrially relevant metabolites—have demonstrated potent antimicrobial properties; however, their antiparasitic potential remains largely unexplored. This study evaluated the anti-trypanocidal activities of extracellular metabolites produced by Streptomyces thermocarboxydus strain Chi-43 (ST-C43) and Streptomyces sp. strain Chi-104 (S-C104) against epimastigote, trypomastigote, and amastigote forms of T. cruzi. The strains were cultured in ISP2 broth, and their extracellular metabolites were assessed via antiparasitic diffusion assays in microplates. The 50% lethal concentration (LC₅₀) values ranged from 102 to 116 μg/mL against epimastigotes and trypomastigotes. The antiparasitic activity was confirmed through 3-(4,5-dimetiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based spectrophotometric assays and optical microscopy. Toxicity assays revealed that the extracellular metabolites were non-toxic to Artemia salina, non-cytotoxic to Huvecs, and non-hemolytic to human erythrocytes. Dose–response regression analysis showed statistically significant differences (p ≤ 0.05). LC-MS/MS analysis identified amphomycin and K-252c aglycone staurosporine as the active antiparasitic compounds. These findings highlight the potential of Streptomyces-derived extracellular metabolites as novel, selective, and safe anti-T. cruzi agents. Nevertheless, further studies in murine or preclinical models are needed to validate their efficacy and support future clinical applications for the treatment of ChD. Full article

Streptomyces spp. are considered a prolific resource of bioactive and structurally diverse secondary metabolites for natural product drug discovery. In this study, 20 out of 56 actinomycetes from soils showed antibacterial activity against at least one tested bacterium. Among them, the CH6 isolate could be a potential source of antibacterial compounds, as indicated by inhibition zone diameters (11.1–32.0 mm) and MIC values (from 8 to 128 µg/mL) against microbial pathogens. The extract showed moderate antioxidant activity against DPPH, hydroxyl, and superoxide anion radicals. Notably, CH6 extract displayed strong inhibitory effects on cancer cells, including MCF-7, A549, HepG2, and HT29, with IC₅₀ values ranging from 18.0 to 73.4 µg/mL, without cytotoxic activity against non-cancerous HEK-293 cells. The genome of CH6 consists of a 6,936,977 bp linear chromosome with a 73.0% GC content, 5831 protein-coding genes, and 13 biosynthetic gene clusters (BGCs). The highest dDDH and ANI values between CH6 and the most closely related type strain, Streptomyces evansiae DSM 41979^T, were 45.8% and 92.6%, respectively, which suggests that CH6 is a novel species. Interestingly, cluster 2, with a size of 133,857 bp, comprised both guangnanmycin and scabichelin clusters, which have been reported for the first time. These findings showed that Streptomyces sp. CH6 could be a novel species and a producer of guangnanmycin and even new secondary metabolites, particularly those with antibacterial and anticancer activities. Full article

With the sustainable increase in agricultural productivity, the need for safer, environmentally friendly pesticide alternatives is also growing. Metabolites of microorganisms (bacteria, fungi, actinomycetes) are emerging as potential bioactive compounds for integrated pest and disease management. These compounds comprise amino acids, carbohydrates, lipids, organic acids, phenolics, peptides, alkaloids, polyketides, and volatile organic compounds. The majority of them have insecticidal, fungicidal, and nematicidal activities. In this review, the classifications, biosynthetic pathways, and ecological functions of primary and secondary metabolites produced by microorganisms are discussed, including their mechanisms of action, ranging from competition to systemic acquired resistance in host plants. The article highlights the importance of microbial genera (viz., Bacillus sp., Pseudomonas sp., Trichoderma sp., Streptomyces sp., etc.) in making chemicals and biopesticides for crop defense. We present the possible applications of microbial biosynthesis strategies and synthetic biology tools in bioprocess development, covering recent innovations in formulation, delivery, and pathway engineering to enhance metabolite production. This review emphasizes the significance of microbial metabolites in improving the plant immunity, yield performance, reduction in pesticide application, and the sustainability of an ecological, sustainable, and resilient agricultural system. Full article

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. Full article

The long regimen of drug therapy, the emergence of drug-resistance (DR), and infections with non-tuberculous mycobacteria (NTMs) are alarming challenges in controlling tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (M.tb), necessitating the pursuit of new, broad-spectrum anti-mycobacterials. With more than two-thirds of the clinically useful antibiotics originating from the bacterial phylum Actinomycetota, and their enormous diversity in India, we explored atypical environments for new bacterial strains with potential anti-M.tb activity. In this study, we the examined the secondary metabolites of soil and endophytic bacterial isolates from the wetland niches of Manipur, India, and determined their anti-mycobacterial properties using viability assays. The ethyl acetate culture filtrate extracts of one of the isolates, named Streptomyces sp. SbAr007, showed broad-spectrum anti-mycobacterial activity against laboratory M.tb strains H37Ra and H37Rv, a clinical drug-resistant M.tb and non-tuberculous mycobacteria (NTM). The isolate was characterized for its phenotype and genetic identity, which indicated its closeness to Streptomyces samsunensis, Streptomyces malaysiensis, and Streptomyces solisilvae. Further, macrophage infection assays showed that the extracts could effectively control the intracellular mycobacterial growth but had negligible cytotoxicity to PBMCs from healthy donors. LC-MS identified an unusual combination of antibiotics in these culture filtrate extracts, which can be further explored for specific active molecules or as a formulation against DR-TB. Full article

Background/Objectives: Grapes (Vitis vinifera), particularly ‘Shine Muscat’, are prone to postharvest quality loss mainly due to poor storage tolerance. Actinomycetes are microbial resources that produce secondary metabolites that exhibit notable functional properties. Methods: This study explored the use of Streptomyces albulus Ah11601 fermentation broth (SFB) as a postharvest treatment to preserve ‘Shine Muscat’ grape quality during 6 days of room temperature storage using physiological, transcriptomic, and bioinformatics analyses to elucidate the underlying regulatory mechanism. Results: The results demonstrated that, compared to the control group stored at room temperature (25 °C) for 6 days (6D), the SFB-treated group (T6D) presented a significant delay in the decrease in fruit hardness and vitamin C content. Further investigations revealed that the 6D treatment significantly elevated lipoxygenase activity, MDA content, O₂⁻ generation rate, and H₂O₂ levels. In addition, both the 6D and T6D treatments significantly increased the activities of SOD and APX. Functional enrichment analysis revealed that the upregulated DEGs in the 6D group were predominantly enriched in pathways such as phenylpropanoid biosynthesis; flavonoid biosynthesis; phenylalanine metabolism; and stilbenoid, diarylheptanoid, and gingerol biosynthesis. The downregulated DEGs were enriched primarily in the endoplasmic reticulum protein processing pathway. In the T6D group, the upregulated DEGs were predominantly enriched in the zeatin biosynthesis pathway. In addition, significant alterations in the expression of genes associated with the ethylene and abscisic acid signaling pathways were detected. Conclusions: In conclusion, SFB treatment effectively mitigated the deterioration of the postharvest quality of ‘Shine Muscat’ grapes by preserving the cellular redox balance, regulating cytokinin and ethylene biosynthesis, and optimizing the regulation of ethylene and abscisic acid signaling. Full article

An Arctic marine-derived strain, MNP-1, was characterized by a combined methodological approach, incorporating a variety of analytical techniques including morphological features, biochemical characteristics, and 16S ribosomal RNA (rRNA) sequence analysis. The chemical investigation of Streptomyces sp. MNP-1 using the OSMAC (one strain many compounds) strategy yielded the isolation of twenty known compounds (1–20), which were unambiguously identified by various spectroscopic approaches including ¹H and ¹³C NMR and ESI-MS (previously reported data). Bioassay results indicated that compounds 2, 3, 5, 9, 14, 15, and 20 had antimicrobial activity against human pathogenic strains including Staphylococcus aureus, Escherichia coli, and Candida albicans with MIC values ranging from 4 to 32 μg/mL, and compounds 3 and 14 exhibited moderate inhibitory activity on A549, MCF-7, and HepG2 tumor lines showing IC₅₀ values within the range of 19.88 to 35.82 µM. These findings suggest that Streptomyces sp. MNP-1 is one of the prolific manufacturers of bioactive secondary metabolites with therapeutic potential. Full article

This study explores the potential anti-H1N1 Influenza A activity of bioactive compounds extracted from Streptomyces ardesiacus, a marine-derived microorganism known for producing diverse secondary metabolites. Four major compounds—1-acetyl-β-carboline, 1H-indole-3-carbaldehyde, anthranilic acid, and indole-3-carboxylic acid—were isolated and characterized through NMR. Among these, the identified structure of 1-acetyl-β-carboline showed the highest IC₅₀ effect, with a dose of 9.71 μg/mL in anti-influenza assays. Using network pharmacology and molecular docking analyses, the interactions of these compounds with key proteins involved in H1N1 pathogenesis were examined. Protein–protein interaction (PPI) networks and Gene Ontology enrichment analysis revealed CDC25B, PARP1, and PTGS2 as key targets, associating these compounds with pathways related to catalytic activity, inflammation, and cell cycle regulation. The molecular docking results demonstrated that 1-acetyl-β-carboline exhibited binding affinities comparable to Tamiflu, the positive control drug, with LibDock scores of 81.89, 77.49, and 89.21 for CDC25B, PARP1, and PTGS2, respectively, compared to Tamiflu’s scores of 84.34, 86.13, and 91.29. These findings highlight the potential of the active compound 1-acetyl-β-carboline from S. ardesiacus as a novel anti-influenza agent, offering insights into their molecular mechanisms of action. The results support further in vitro and in vivo studies to validate the observed inhibitory mechanisms and therapeutic applications against H1N1 Influenza A. Full article

Potato common scab, caused by Streptomyces species, is a widespread soil-borne disease that poses a significant threat to potato cultivation globally. In this study, a Bacillus velezensis D7-8 strain was isolated from a potato. This endophytic bacterium exhibited broad-spectrum antifungal activity, and pot trials demonstrated that the D7-8 strain effectively controlled potato common scab with an efficacy of 42.07%. The complete genome sequence of the D7-8 strain was sequenced and subsequently identified as B. velezensis through multiple bioinformatic methods, primarily through structural variation analysis of whole-genome sequences. The machine learning method predicted that the expression profiles of colinear genes among closely related Bacillus species were highly consistent. Metabolite analysis of crude extracts using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive HRMS) revealed that D7-8 produces bioactive compounds, including surfactin and fengycin, both known for their antimicrobial properties. This study elucidates the antagonistic effect of B. velezensis D7-8 against Streptomyces acidiscabies and provides a valuable reference for future research on accurate microbial identification. Full article

The objective of this study was to optimise the potato dextrose agar (PDA) culture medium in terms of its potential for use in the growth of actinobacteria. The strain used in this study was a species of actinobacteria previously identified as Streptosporangium sp. (P1C3), characterised by slow growth (20 days of incubation), low aerial mycelium production, and no pigment production. To determine the optimal formulation, the Streptosporangium sp. (P1C3) strain was tested for incubation time and aerial mycelium growth across 27 formulations based on the PDA culture medium. A central composite rotational design (CCRD) experimental methodology was employed, where glucose concentration (g/L), yeast extract concentration (g/L), pH, and temperature were tested. Among the tested formulations, 01, 05, 09, and 13 showed a reduction in incubation time and complete aerial mycelium growth, which was linearly influenced by the four tested variables. Response surface analysis indicated that the optimal values for promoting aerial mycelium growth in the shortest incubation time were 10 g/L glucose concentration, from 1 g/L to 3 g/L yeast extract concentration, pH levels between 5.7 and 7.2, and temperatures between 24 °C and 32 °C. The optimisation of the PDA medium proved effective in improving the isolation of actinobacteria and enhancing the production of metabolites with potential antimicrobial activity. Full article

Microbial secondary metabolites (SMs) serve as the main source of natural antibiotics. Bioinformatics analyses reveal that multiple secondary metabolites biosynthetic gene clusters (BGCs) exist in the genomes of fungi and bacteria but the vast majority remains silent due to the control of intricate regulatory networks. An in-depth comprehension of these regulatory processes is required for the activation of cryptic gene clusters. Among them, the regulations at the proteomic level originating from epigenetic modifications and their correlations with secondary metabolite biosynthesis have gained increasing interest recently, especially the modifications on bacterial nucleoid-associated proteins. This article highlights the recent advances and important roles of bacterial nucleoid-associated proteins (NAPs) in the biosynthesis of SMs. Developing new tools around NAPs would be significant for the discovery of novel bioactive compounds in microbial resources. Full article