Metabolite profiling of Malaysian Gracilaria edulis reveals Eplerenone as novel antibacterial compound for drug repurposing against MDR Bacteria
Ontology highlight
ABSTRACT:
ORGANISM(S): Gracilaria Edulis
TISSUE(S): Seaweed
PROVIDER: ST001839 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:With a continuous threat of antimicrobial resistance on human health worldwide, efforts for new alternatives are ongoing for the management of bacterial infectious diseases. Natural products of land and sea, being conceived to be having fewer side effects, pose themselves as a welcome relief. In this respect, we have taken a scaffolded approach to unearthing the almost unexplored chemical constituents of Malaysian red seaweed, Gracilaria edulis. Essentially, a preliminary evaluation of the ethyl acetate and acetone solvent extracts, among a series of six such, revealed potential antibacterial activity against six MDR species namely, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, and Bacillus subtilis. Detailed analyses of the inlying chemical constituents, through LC-MS and GC-MS chromatographic separation, revealed a library of metabolic compounds. These were led for further virtual screening against selected key role playing proteins in the virulence of the aforesaid bacteria. To this end, detailed predictive pharmacological analyses added up to reinforce Eplerenone as a natural alternative from the plethora of plausible bioactives. Our work adds the ongoing effort to re-discover and repurpose biochemical compounds to combat the antimicrobial resistance offered by the Gram-positive and the -negative bacterial species.
| S-EPMC8279767 | biostudies-literature
Project description:Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to elucidate affected biochemical pathways downstream of monoamine reuptake inhibition by interrogating metabolomic profiles in DBA/2Ola mice after chronic paroxetine treatment. Metabolomic changes were investigated using gas chromatography-mass spectrometry profiling and group differences were analyzed by univariate and multivariate statistics. Pathways affected by antidepressant treatment were related to energy metabolism, amino acid metabolism and hormone signaling. The identified pathways reveal further antidepressant therapeutic action and represent targets for drug development efforts. A comparison of the central nervous system with blood plasma metabolite alterations identified GABA, galactose-6-phosphate and leucine as biomarker candidates for assessment of antidepressant treatment effects in the periphery.
| S-EPMC3309495 | biostudies-literature
Project description:The current epidemic of antibiotic-resistant infections urges to develop alternatives to less-effective antibiotics. To assess anti-bacterial potential, a novel coordinate compound (RU-S4) was synthesized using ruthenium-Schiff base-benzimidazole ligand, where ruthenium chloride was used as the central atom. RU-S4 was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy. Antibacterial effect of RU-S4 was studied against Staphylococcus aureus (NCTC 8511), vancomycin-resistant Staphylococcus aureus (VRSA) (CCM 1767), methicillin-resistant Staphylococcus aureus (MRSA) (ST239: SCCmecIIIA), and hospital isolate Staphylococcus epidermidis. The antibacterial activity of RU-S4 was checked by growth curve analysis and the outcome was supported by optical microscopy imaging and fluorescence LIVE/DEAD cell imaging. In vivo (balb/c mice) infection model prepared with VRSA (CCM 1767) and treated with RU-S4. In our experimental conditions, all infected mice were cured. The interaction of coordination compound with bacterial cells were further confirmed by cryo-scanning electron microscope (Cryo-SEM). RU-S4 was completely non-toxic against mammalian cells and in mice and subsequently treated with synthesized RU-S4.
| S-EPMC7178087 | biostudies-literature
Project description:Background: Cyanobacteria are ecologically significant prokaryotes that can be found in heavy metals contaminated environments. As their photosynthetic machinery imposes high demands for metals, homeostasis of these micronutrients has been extensively considered in cyanobacteria. Recently, most studies have been focused on different habitats using microalgae leads to a remarkable reduction of an array of organic and inorganic nutrients, but what takes place in the extracellular environment when cells are exposed to external supplementation with heavy metals remains largely unknown. Methods: Here, extracellular polymeric substances (EPS) production in strains Nostoc sp. N27P72 and Nostoc sp. FB71 was isolated from different habitats and thenthe results were compared and reported . Result: Cultures of both strains, supplemented separately with either glucose, sucrose, lactose, or maltose showed that production of EPS and cell dry weight were boosted by maltose supplementation. The production of EPS (9.1 ± 0.05 μg/ml) and increase in cell dry weight (1.01 ± 0.06 g/l) were comparatively high in Nostoc sp. N27P72 which was isolated from lime stones.The cultures were evaluated for their ability to remove Cu (II), Cr (III), and Ni (II) in culture media with and without maltose. The crude EPS showed metal adsorption capacity assuming the order Ni (II)> Cu (II)> Cr (III) from the metal-binding experiments .Nickel was preferentially biosorbed with a maximal uptake of 188.8 ± 0.14 mg (g cell dry wt) -1 crude EPS. We found that using maltose as a carbon source can increase the production of EPS, protein, and carbohydrates content and it could be a significant reason for the high ability of metal absorbance. FT-IR spectroscopy revealed that the treatment with Ni can change the functional groups and glycoside linkages in both strains. Results of Gas Chromatography-Mass Spectrometry (GC–MS) were used to determine the biochemical composition of Nostoc sp. N27P72, showed that strong Ni (II) removal capability could be associated with the high silicon containing heterocyclic compound and aromatic diacid compounds content.
2022-01-24 | PXD030537 | Pride
Project description:Background: Cyanobacteria are ecologically significant prokaryotes that can be found in heavy metals contaminated environments. As their photosynthetic machinery imposes high demands for metals, homeostasis of these micronutrients has been extensively considered in cyanobacteria. Recently, most studies have been focused on different habitats using microalgae leads to a remarkable reduction of an array of organic and inorganic nutrients, but what takes place in the extracellular environment when cells are exposed to external supplementation with heavy metals remains largely unknown. Methods: Here, extracellular polymeric substances (EPS) production in strains Nostoc sp. N27P72 and Nostoc sp. FB71 was isolated from different habitats and thenthe results were compared and reported . Result: Cultures of both strains, supplemented separately with either glucose, sucrose, lactose, or maltose showed that production of EPS and cell dry weight were boosted by maltose supplementation. The production of EPS (9.1 ± 0.05 μg/ml) and increase in cell dry weight (1.01 ± 0.06 g/l) were comparatively high in Nostoc sp. N27P72 which was isolated from lime stones.The cultures were evaluated for their ability to remove Cu (II), Cr (III), and Ni (II) in culture media with and without maltose. The crude EPS showed metal adsorption capacity assuming the order Ni (II)> Cu (II)> Cr (III) from the metal-binding experiments .Nickel was preferentially biosorbed with a maximal uptake of 188.8 ± 0.14 mg (g cell dry wt) -1 crude EPS. We found that using maltose as a carbon source can increase the production of EPS, protein, and carbohydrates content and it could be a significant reason for the high ability of metal absorbance. FT-IR spectroscopy revealed that the treatment with Ni can change the functional groups and glycoside linkages in both strains. Results of Gas Chromatography-Mass Spectrometry (GC–MS) were used to determine the biochemical composition of Nostoc sp. N27P72, showed that strong Ni (II) removal capability could be associated with the high silicon containing heterocyclic compound and aromatic diacid compounds content. Conclusion: The results of this studyindicatede that strains Nostoc sp. N27P72 can be a good candidate for the commercial production of EPS and might be utilized in bioremediation field as an alternative to synthetic and abiotic flocculants.
2022-01-24 | PXD030535 | Pride
Project description:The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal-based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram-positive bacteria, including multi-drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number of genes related to metal transport and homeostasis were upregulated upon short treatment of the cells with gold compound. Toxicity tests conducted on precision-cut mouse tissue slices ex vivo revealed that the organogold compound is poorly toxic to mouse liver and kidney tissues, and may thus, be treated as an antibacterial drug candidate.
| S-EPMC8518660 | biostudies-literature
Project description:This study was designed to propose alternative therapeutic compounds to fight against bacterial pathogens. Thus, a library of nitrogen-based compounds bis(triazolyl)methane (1T-7T) and bis(pyrazolyl)methane (1P-11P) was synthesised following previously reported methodologies and their antibacterial activity was tested using the collection strains of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Moreover, the novel compound 2P was fully characterized by IR, UV-Vis and NMR spectroscopy. To evaluate antibacterial activity, minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) assays were carried out at different concentrations (2-2000 µg/mL). The MTT assay and Resazurin viability assays were performed in both human liver carcinoma HepG2 and human colorectal adenocarcinoma Caco-2 cell lines at 48 h. Of all the synthesised compounds, 2P had an inhibitory effect on Gram-positive strains, especially against S. aureus. The MIC and MBC of 2P were 62.5 and 2000 µg/mL against S. aureus, and 250 and 2000 µg/mL against E. faecalis, respectively. However, these values were > 2000 µg/mL against E. coli and P. aeruginosa. In addition, the MBICs and MBECs of 2P against S. aureus were 125 and > 2000 µg/mL, respectively, whereas these values were > 2000 µg/mL against E. faecalis, E. coli, and P. aeruginosa. On the other hand, concentrations up to 250 µg/mL of 2P were non-toxic doses for eukaryotic cell cultures. Thus, according to the obtained results, the 2P nitrogen-based compound showed a promising anti-Gram-positive effect (especially against S. aureus) both on planktonic state and biofilm, at non-toxic concentrations.
| S-EPMC8357914 | biostudies-literature
Project description:Nontargeted metabolomics methods have increased potential to identify new disease biomarkers, but assessments of the additive information provided in large human cohorts by these less biased techniques are limited. To diversify our knowledge of diabetes-associated metabolites, we leveraged a method that measures 305 targeted or "known" and 2,342 nontargeted or "unknown" compounds in fasting plasma samples from 2,750 participants (315 incident cases) in the Jackson Heart Study (JHS)-a community cohort of self-identified African Americans-who are underrepresented in omics studies. We found 307 unique compounds (82 known) associated with diabetes after adjusting for age and sex at a false discovery rate of <0.05 and 124 compounds (35 known, including 11 not previously associated) after further adjustments for BMI and fasting plasma glucose. Of these, 144 and 68 associations, respectively, replicated in a multiethnic cohort. Among these is an apparently novel isomer of the 1-deoxyceramide Cer(m18:1/24:0) with functional geonomics and high-resolution mass spectrometry. Overall, known and unknown metabolites provided complementary information (median correlation ρ = 0.29), and their inclusion with clinical risk factors improved diabetes prediction modeling. Our findings highlight the importance of including nontargeted metabolomics methods to provide new insights into diabetes development in ethnically diverse cohorts.
| S-EPMC9630088 | biostudies-literature
Project description:Pathogenic bacterial biofilms play an important role in recurrent nosocomial and medical device-related infections. Once occurred, the complex structure of the biofilm promotes the development of antibiotic resistance and becomes extremely difficult to eradicate. Here we describe a novel and effective anti-biofilm compound maipomycin A (MaiA), which was isolated from the metabolites of a rare actinomycete strain Kibdelosporangium phytohabitans XY-R10. Its structure was deduced from analyses of spectral data and confirmed by single-crystal X-ray crystallography. This natural product demonstrated a broad spectrum of anti-biofilm activities against Gram-negative bacteria. Interestingly, the addition of Fe(II) or Fe(III) ions could block the biofilm inhibition activity of MaiA because it is an iron chelator. However, not all iron chelators showed biofilm inhibition activity, suggesting that MaiA prevents biofilm formation through a specific yet currently undefined pathway. Furthermore, MaiA acts as a synergist to enhance colistin efficacy against Acinetobacter baumannii. Our results indicate that MaiA may potentially serve as an effective antibiofilm agent to prevent Gram-negative biofilm formation in future clinical applications.
| S-EPMC7835661 | biostudies-literature
Project description:Although MALDI-ToF platforms for microbial identifications have found great success in clinical microbiology, the sole use of protein fingerprints for the discrimination of closely related species, strain-level identifications, and detection of antimicrobial resistance remains a challenge for the technology. Several alternative mass spectrometry-based methods have been proposed to address the shortcomings of the protein-centric approach, including MALDI-ToF methods for fatty acid/lipid profiling and LC-MS profiling of metabolites. However, the molecular diversity of microbial pathogens suggests that no single "ome" will be sufficient for the accurate and sensitive identification of strain- and susceptibility-level profiling of bacteria. Here, we describe the development of an alternative approach to microorganism profiling that relies upon both metabolites and lipids rather than a single class of biomolecule. Single-phase extractions based on butanol, acetonitrile, and water (the BAW method) were evaluated for the recovery of lipids and metabolites from Gram-positive and -negative microorganisms. We found that BAW extraction solutions containing 45% butanol provided optimal recovery of both molecular classes in a single extraction. The single-phase extraction method was coupled to hydrophilic interaction liquid chromatography (HILIC) and ion mobility-mass spectrometry (IM-MS) to resolve similar-mass metabolites and lipids in three dimensions and provide multiple points of evidence for feature annotation in the absence of tandem mass spectrometry. We demonstrate that the combined use of metabolites and lipids can be used to differentiate microorganisms to the species- and strain-level for four of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa) using data from a single ionization mode. These results present promising, early stage evidence for the use of multiomic signatures for the identification of microorganisms by liquid chromatography, ion mobility, and mass spectrometry that, upon further development, may improve upon the level of identification provided by current methods.
| S-EPMC10885331 | biostudies-literature