Identification of Potential Antimicrobial Compounds from a Marine Streptomyces sp. SM2.4 Strain (MH752437) Isolated from Rachgoun Island in Western Algeria

14 páginas.- 4 figuras.- 8 tablas.- 60 referenciasBackground: Marine actinobacteria are a potential resource for natural products; their secondary bioactive metabolites have shown several biological activities. Most of the isolated and identified actinobacteria in Algeria were usually explored from caves, Saharan soil or palm groves. The marine ecosystem is poorly explored and documented. Methods: Five Streptomyces strains producing bioactive compounds were isolated from Rachgoun Island located in Western Algeria and characterised phenotypically and genotypically using microbiological and 16S rRNA sequencing methods, respectively. The crude extract of the most representative strain ¿Streptomyces sp. strain SM2.4¿ and its seven active fractions were characterised by GC/MS analysis. Results: Streptomyces sp. strain SM2.4 revealed the strongest activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, the fungus Aspergillus niger and was inactive against Gram-negative bacteria. GC/MS analysis of the methylated crude extract of Streptomyces sp. strain SM2.4 revealed the presence of 11 major compounds including fatty acids methyl ester (12-methyltridecanoic acid methyl ester, 9-hexadecenoic acid methyl ester, hexadecanoic acid methyl ester, 14-methylhexadecanoic acid methyl ester and 16-methylheptadecanoic acid methyl ester), 2,4-di-tert-butylphenol, (4S,4aS,8aR)-4,8a-dimethyloctahydro-4a(2H)-naphthalenol (geosmin), 2,4-dimethylbenzaldehyde, 3,4-difluorobenzaldehyde, dimethylfuran-2,4-dicarboxylate and pyrrolo(1,2-a)pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)-. Partial purification of the crude extract by Thin-layer chromatography provided seven active fractions which were tested by radial diffusion assay. GC/MS analysis of the active TLC-fractions revealed the presence of a mixture of active compounds from which 2-(bromomethyl)-2-(2-methylphenyl)-1,3-dioxolane was found to be a new 1,3 dioxolane derivative. Furthermore, 3,4-dimethylbenzamide and pyrido[2,3-d] pyridazine-1,4-dione, hexahydro-3-(2-methylpropyl)-, were extracted for the first time from a natural source. Conclusion: Our study reveals that marine Streptomyces sp. strain SM2.4 has an interesting antimicrobial potential due to its panel of bioactive compounds.Peer reviewe

Comparative Computational Analysis of Dirithromycin and Azithromycin in Search for a Potent Drug against COVID-19 caused by SARS-CoV-2: Evidence from molecular docking and dynamic simulation

Due to the emergency and uncontrolled situation caused by the COVID-19 pandemic that arising in the entire world, it is necessary to choose available drugs that can inhibit or prevent the disease. Therefore, the repurposing of the commercial antibiotic, dirithromycin has been screened for the first time against fifteen receptors and compared to the azithromycin using a molecular docking approach to identify possible SARS-CoV-2 inhibitors. Our docking results showed that dirithromycin fit significantly in the Furin catalytic pocket having the lowest binding score (-9.9 Kcal/mol) with respect to azithromycin (-9.4 Kcal/mol) and can interact and block both Asp154 and Ser368 residues by Van der Walls interaction as well as bound to His194 and Ser368 residues via hydrogen bonds. Good results were also obtained with the Tmprss-2 receptor. A Molecular Dynamic simulation was assessed to confirm this interaction. Additionally, detailed receptor-ligand interactions with SARS-CoV-2 and pro-inflammatory mediators were investigated suggesting more target information with interesting results. The findings of this study are very efficient and provide a basis for the development of dirithromycin for clinical trial applications to be efficient in treating SARS-CoV-2 infections

Multi-Solvent Extraction Procedure for the Pioneer Fecal Metabolomic Analysis—Identification of Potential Biomarkers in Stable Kidney Transplant Patients

Metabolic alteration plays a functional role in kidney allograft complications. Metabolomics is a promising high-throughput approach in nephrology but is still limited by the lack of overlap in metabolite coverage. We performed an untargeted fecal metabolomic analysis of forty stable kidney allograft recipients and twenty non-transplant controls. First, we applied the ultra-high performance liquid chromatography (UHPLC) analysis coupled with the Diod Array detector. The potential biomarkers were then collected and identified by gas chromatography-mass spectrometry (GCMS). In order to allow for complete coverage of the fecal polar and non-polar metabolites, the performance of five organic solvents with increasing polarity was investigated successively. UHPLC analysis revealed that the fecal metabolite profiles following the five extractions were significantly different between controls and kidney allografts. GC-MS analysis showed that the best predictors’ metabolites belonged mainly to long-chain fatty acids, phenolic compounds, and amino acids. Collectively, our results showed the efficiency of our pioneer method to successfully discriminate stable kidney-transplant recipients from controls. These findings suggest that distinct metabolic profiles mainly affect fatty acid biosynthesis and amino acid metabolism. In such a context, the novel insights into metabolomic investigation may be a valuable tool that could provide useful new relevant biomarkers for preventing kidney transplant complications

Isolation, Characterization and Chemical Synthesis of Large Spectrum Antimicrobial Cyclic Dipeptide (l-leu-l-pro) from Streptomyces misionensis V16R3Y1 Bacteria Extracts. A Novel 1H NMR Metabolomic Approach

International audienceStreptomyces is the most frequently described genus of Actinomycetes, a producer of biologically active secondary metabolites. Indeed, the Streptomyces species produces about 70% of antibiotics and 60% of antifungal molecules used in agriculture. Our study was carried out with the goal of isolating and identifying antimicrobial secondary metabolites from Streptomyces misionensis V16R3Y1 isolated from the date palm rhizosphere (southern Tunisia). This strain presented a broad range of antifungal activity against Fusarium oxysporum, Aspergillus flavus, Penicillium expansum, Aspergillus niger, Candida albicans, Candida metapsilosis, and Candida parapsilosis and antibacterial activity against human pathogenic bacteria, including Escherichia fergusonii, Staphylococcus aureus, Salmonella enterica, Enterococcus faecalis, Bacillus cereus and Pseudomonas aeruginosa. The purification procedure entailed ethyl acetate extract, silica gel column, and thin layer chromatography. Based on 1H NMR metabolomic procedure application, also supported by the GC-MS analysis, cyclic dipeptide (l-Leucyl-l-Proline) was identified as the major compound in the bioactive fraction. In order to confirm the identity of the active compound and to have a large quantity thereof, a chemical synthesis of the cyclic dipeptide was performed. The synthetic compound was obtained with a very good yield (50%) and presented almost the same effect compared to the extracted fraction. This study indicates for the first time that Streptomyces misionensis V16R3Y1 exhibits a broad spectrum of antimicrobial activities, produced cyclic dipeptide (l-Leucyl-l-Proline) and might have potential use as a natural agent for pharmaceutical and agri-food applications

Tripeptides from Allium subhirsitum L. extracts: Pharmacokinetics properties, toxicity prediction and in silico study against SARS-CoV-2 enzymes and pro-inflammatory proteins

Developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities is urgently needed to combat emerging human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since no available clinically antiviral drugs have been approved to eradicate COVID-19 as of the writing of this report, this study aimed to investigate bioactive short peptides from Allium subhirsutum L. (Hairy garlic) extracts identified through HR-LC/MS analysis that could potentially hinder the multiplication cycle of SARS-CoV-2 via molecular docking study. The obtained promising results showed that the peptides (Asn-Asn-Asn) possess the highest binding affinities of -8.4 kcal/mol against S protein, (His-Phe-Gln) of -9.8 kcal/mol and (Gln-His-Phe) of -9.7 kcal/mol towards hACE2, (Thr-Leu-Trp) of -10.3 kcal/mol and (Gln-Phe-Tyr) of -9.8 kcal/mol against furin. Additionally, the identified peptides show strong interactions with the targeted and pro-inflammatory ranging from -8.1 to -10.5 kcal/mol for NF−κB-inducing kinase (NIK), from -8.2 to -10 kcal/mol for phospholipase A2 (PLA2), from -8.0 to -10.7 kcal/mol for interleukin-1 receptor-associated kinase 4 (IRAK-4), and from -8.6 to -11.6 kcal/mol for the cyclooxygenase 2 (COX2) with Gln-Phe-Tyr model seems to be the most prominent. Results from pharmacophore, drug-likeness and ADMET prediction analyses clearly evidenced the usability of the peptides to be developed as an effective drug, beneficial for COVID-19 treatment