Integrative proteomics and metabolomics approach to elucidate the antimicrobial effect of simvastatin on <scp><i>Escherichia coli</i></scp>

Koçak, Engin; Nemutlu, Emirhan; Kır, Sedef; Sağıroğlu, Meral; Özkul, Ceren

doi:10.1002/bmc.5180

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…After drying, samples were methoxylated and derivatized as described previously. 8 , 9 After the addition of 20 μL methoxyamine hydrochloride (20 mg/mL in pyridine), all samples were incubated for 90 minutes at 30°C. Finally, N-methyl-N-(trimethylsilyl)-trifluoroacetamide solution including 1% trimethylchlorosilane was added, and then the samples were incubated at 37°C for 30 minutes.…”

Section: Methodsmentioning

confidence: 99%

Comparative Metabolomic Profiles of Vascular Involvement in Behçet’s Disease

2023

Eur J Rheumatol

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Background: Behçet’s disease is a systemic, inflammatory disease affecting multiple organs. Vascular involvement is the main cause of morbidity and mortality in Behçet’s disease patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidence in this patient group. The aim of this study is to investigate the unique metabolic signatures of Behçet’s disease patients with vascular involvement. Methods: Metabolomic profiling was performed on serum samples of 48 Behçet’s disease patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometry-based untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways. Results: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of Behçet’s disease, vascular involvement in Behçet’s disease, and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis, could be an important stage for developing Behçet’s disease. Conclusion: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of Behçet’s disease pathogenesis and also developing vascular involvement in Behçet’s disease at the metabolite level. The results showed that vascular involvement in Behçet’s disease could be highly linked with amino acid metabolism and also the antioxidant system, and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of Behçet’s disease and also for vascular involvement in Behçet’s disease.

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Section: Methodsmentioning

confidence: 99%

Comparative Metabolomic Profiles of Vascular Involvement in Behçet’s Disease

2023

Eur J Rheumatol

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“…In addition, statins show antimicrobial activity, as has been shown in several studies [ 91 , 92 , 93 ]. In a recent study, for the first time, the antimicrobial effect of simvastatin was evaluated on proteome and metabolome in Escherichia coli by LC-MS-based label-free proteomic analysis and GC-MS-based metabolomics [ 94 ]. Differentially expressed proteins and metabolites between control and simvastatin-treated groups were measured to find altered molecules under the simvastatin stress condition.…”

Section: Lipid-lowering Therapies and Metabolomicsmentioning

confidence: 99%

“…Therefore, simvastatin caused increased reactive oxygen species (ROS) production and a significant change in the energy metabolism of Escherichia coli to adapt to stress conditions. These integrated metabolomics and proteomics data allowed a global evaluation of the simvastatin effects on the phenotype of Escherichia coli suggesting some important antimicrobial targets and cellular pathways involved in the response to stress conditions, thus providing more details in the comprehension of the mechanisms of action for simvastatin on various biological pathways [ 94 ]. This paper is an example of the use of metabolomics for drug repurposing, also known as drug repositioning, which is an efficient strategy for identifying new pharmacological activities or therapeutic purposes for already-approved or investigational drugs that are different from the original medical indications [ 95 , 96 ].…”

Section: Lipid-lowering Therapies and Metabolomicsmentioning

confidence: 99%

Pharmacometabolomics for the Study of Lipid-Lowering Therapies: Opportunities and Challenges

Gianazza

Brioschi

Iezzi

et al. 2023

IJMS

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Lipid-lowering therapies are widely used to prevent the development of atherosclerotic cardiovascular disease (ASCVD) and related mortality worldwide. “Omics” technologies have been successfully applied in recent decades to investigate the mechanisms of action of these drugs, their pleiotropic effects, and their side effects, aiming to identify novel targets for future personalized medicine with an improvement of the efficacy and safety associated with the treatment. Pharmacometabolomics is a branch of metabolomics that is focused on the study of drug effects on metabolic pathways that are implicated in the variation of response to the treatment considering also the influences from a specific disease, environment, and concomitant pharmacological therapies. In this review, we summarized the most significant metabolomic studies on the effects of lipid-lowering therapies, including the most commonly used statins and fibrates to novel drugs or nutraceutical approaches. The integration of pharmacometabolomics data with the information obtained from the other “omics” approaches could help in the comprehension of the biological mechanisms underlying the use of lipid-lowering drugs in view of defining a precision medicine to improve the efficacy and reduce the side effects associated with the treatment.

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“…400 μL supernatant was evaporated overnight at 4°C using a vacuum centrifuge. The dried samples were methoxylated and derivatized as described previously (8,9). 20 μL of methoxyamine hydrochloride (20 mg/mL in pyridine) was added, and the samples were incubated 90 minutes at 30°C.…”

Section: Metabolomics Sample Preparation Analysismentioning

confidence: 99%

Comparative Metabolomic Profiles of Vascular Involvement in Behçet’s Disease

Yücel

Sertoğlu

Omma

et al. 2023

Preprint

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Aim: Behçet’s disease (BD) is a chronic, inflammatory disease effecting multiple organs. Vascular involvement is a major cause of morbidity and mortality in BD patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidences in this patient group. The aim of the current study is to investigate the unique metabolic signatures of BD patients with vascular involvement (VBD). Methods: Metabolomic profiling was performed on serum samples of 48 BD patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways. Results: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of BD, vascular involvement in BD and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis could be an important stage for developing BD. Conclusion: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of BD pathogenesis and also developing vascular involvement in BD at the metabolite level. The results showed that vascular involvement in BD could be highly linked with amino acid metabolism and also the antioxidant system and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of BD and also for vascular involvement in BD.

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Integrative proteomics and metabolomics approach to elucidate the antimicrobial effect of simvastatin on Escherichia coli

Cited by 7 publications

References 41 publications

Comparative Metabolomic Profiles of Vascular Involvement in Behçet’s Disease

Comparative Metabolomic Profiles of Vascular Involvement in Behçet’s Disease

Pharmacometabolomics for the Study of Lipid-Lowering Therapies: Opportunities and Challenges

Comparative Metabolomic Profiles of Vascular Involvement in Behçet’s Disease

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