Integration of metabolomics and transcriptomics indicates changes in MRSA exposed to terpinen-4-ol
Ontology highlight
ABSTRACT: Background
This study investigated the effects of terpinen-4-ol on methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, and the possible mechanisms governing this effect. Results
We observed that terpinen-4-ol has good antibacterial activity and inhibits the formation of MRSA biofilm. The MIC and MBC values for terpinen-4-ol against S. aureus were 0.08% ~ 0.32%. And terpinen-4-ol at 0.32% could kill all bacteria and clear all biofilms. Untargeted metabolomic and transcriptomic analyses showed that terpinen-4-ol strongly inhibited DNA and RNA biosynthesis in MRSA at 2 h after treatment by affecting genes and metabolites related to purine and pyrimidine metabolic pathways. Some differential genes which play important roles in DNA synthesis and the production of eDNA from biofilm exposed to terpinen-4-ol was also significantly decreased compared with that of the control. Conclusions
Terpinen-4-ol has good antibacterial activity and significantly inhibits the formation of MRSA biofilm by inhibiting purine and pyrimidine metabolism.
SUBMITTER: Cheng F
PROVIDER: S-EPMC8566654 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Staphylococcus aureus (S. aureus) is a gram-positive bacterium that causes a wide range of diseases. Terpinen-4-ol is a monoterpene component contained in most plant essential oils with good antibacterial activity. In this study, terpinen-4-ol effectively inhibited 13 strains of S. aureus, and effectively inhibited the biofilm of MRSA. Metabolomics and transcriptomics were used to elucidate changes in MRSA cells exposed to terpinen-4-ol. Terpinen-4-ol significantly changed (greater than a 2- or less than a 2-fold change) the expression of 304 genes and the level of 847 metabolites (greater than a 1.5- or less than a 0.67-fold change) in MRSA. The levels of genes and metabolites related to the valine, leucine and isoleucine biosynthesis metabolism pathway, the purine and pyrimidine metabolism pathway, energy metabolism and β-lactam resistance were dramatically changed in biofilms exposed to terpinen-4-ol. To the best of our knowledge, this research is the first to report the metabolite and expression profiles of MRSA exposed to terpinen-4-ol.
2020-09-09 | GSE157638 | GEO
Project description:Integration of Metabolomics and Transcriptomics Reveals Changes in MRSA Exposed to Terpinen-4-ol
| PRJNA662311 | ENA
Project description:Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the GABAA receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.
| S-EPMC4142302 | biostudies-literature
Project description:Staphylococcus aureus is able to rapidly develop mechanisms of resistance to various drugs and to form strong biofilms, which makes it necessary to develop new antibacterial drugs. The essential oil of Melaleuca alternifolia is used as an antibacterial, a property believed to be mainly due to the presence of terpinen-4-ol. Based on this, the objective of this study was to evaluate the antibacterial and antibiofilm potential of terpinen-4-ol against S. aureus. The Minimal Inhibitory and Minimal Bactericidal Concentrations (MIC and MBC) of terpinen-4-ol were determined, and the effect of its combination with antibacterial drugs as well as its activity against S. aureus biofilms were evaluated. In addition, an in silico analysis of its pharmacokinetic parameters and a molecular docking analysis were performed. Terpinen-4-ol presented a MIC of 0.25% (v/v) and an MBC of 0.5% (v/v) (bactericidal action); its association with antibacterials was also effective. Terpinen-4-ol has good antibiofilm activity, and the in silico results indicated adequate absorption and distribution of the molecule in vivo. Molecular docking indicated that penicillin-binding protein 2a is a possible target of terpinen-4-ol in S. aureus. This work highlights the good potential of terpinen-4-ol as an antibacterial product and provides support for future pharmacological studies of this molecule, aiming at its therapeutic application.
| S-EPMC7350221 | biostudies-literature
Project description:CYP102A1 from Bacillus megaterium is an important enzyme in biotechnology, because engineered CYP102A1 enzymes can react with diverse substrates and produce human cytochrome P450-like metabolites. Therefore, CYP102A1 can be applied to drug metabolite production. Terpinen-4-ol is a cyclic monoterpene and the primary component of essential tea tree oil. Terpinen-4-ol was known for therapeutic effects, including antibacterial, antifungal, antiviral, and anti-inflammatory. Because terpenes are natural compounds, examining novel terpenes and investigating the therapeutic effects of terpenes represent responses to social demands for eco-friendly compounds. In this study, we investigated the catalytic activity of engineered CYP102A1 on terpinen-4-ol. Among CYP102A1 mutants tested here, the R47L/F81I/F87V/E143G/L188Q/N213S/E267V mutant showed the highest activity to terpinen-4-ol. Two major metabolites of terpinen-4-ol were generated by engineered CYP102A1. Characterization of major metabolites was confirmed by liquid chromatography-mass spectrometry (LC-MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopy (NMR). Based on the LC-MS results, the difference in mass-to-charge ratio of an ion (m/z) between terpinen-4-ol and its major metabolites was 16. One major metabolite was defined as 1,4-dihydroxy-p-menth-2-ene by NMR. Given these results, we speculate that another major metabolite is also a mono-hydroxylated product. Taken together, we suggest that CYP102A1 can be applied to make novel terpene derivatives.
| S-EPMC11016761 | biostudies-literature
Project description:While recent advances in metabolomic measurement technologies have been dramatic, extracting biological insight from complex metabolite profiles remains a challenge. We present an analytical strategy that uses data obtained from high resolution liquid chromatography-mass spectrometry and a bioinformatics toolset for detecting actively changing metabolic pathways upon external perturbation. We begin with untargeted metabolite profiling to nominate altered metabolites and identify pathway candidates, followed by validation of those pathways with transcriptomics. Using the model organisms Rhodospirillum rubrum and Bacillus subtilis, our results reveal metabolic pathways that are interconnected with methionine salvage. The rubrum-type methionine salvage pathway is interconnected with the active methyl cycle in which re-methylation, a key reaction for recycling methionine from homocysteine, is unexpectedly suppressed; instead, homocysteine is catabolized by the transsulfuration pathway. Notably, the non-mevalonate pathway is repressed, whereas the rubrum-type methionine salvage pathway contributes to isoprenoid biosynthesis upon 5'-methylthioadenosine feeding. In this process, glutathione functions as a coenzyme in vivo when 1-methylthio-d-xylulose 5-phosphate (MTXu 5-P) methylsulfurylase catalyzes dethiomethylation of MTXu 5-P. These results clearly show that our analytical approach enables unexpected metabolic pathways to be uncovered.
| S-EPMC4334135 | biostudies-literature
Project description:Background and Objectives: Trifarotene is a topical retinoid selective for retinoic acid receptor gamma that was recently approved for treatment of acne vulgaris. We performed a gene expression analysis to identify the molecular and cellular impact of trifarotene treatment on acne papules. Methods: In this open-label prospective study, subjects with moderate inflammatory acne of the back were treated with trifarotene 0.005% or vehicle cream on dedicated areas for 27 days, and 4 biopsies were collected from each subject (1 from skin without a visible acne lesion and three at the site of an acne papule: one baseline, one after vehicle treatment, and one after trifarotene treatment). Large scale gene expression profiling of the biopsies was performed using Affymetrix technology, treatment-specific gene expression profiles were generated using statistical modeling, and pathway analysis was performed. Using single-cell RNAseq data, in silico deconvolution of transcriptomics data was performed to identify cellular signatures. Results: We discovered a unique set of 67 genes modulated by trifarotene that are primarily involved in cellular migration, inflammation, and extracellular matrix reorganization. Changes in cellular expression were similar in both trifarotene-treated and spontaneously-resolving lesions. However, only trifarotene treatment impacted SPP1+ macrophages, a subset of highly proliferative macrophages recently identified in fibrotic tissue. Conclusions: These results show that trifarotene has a novel action in acne treatment by affecting epidermal and immune components of acne pathogenesis.
| S-EPMC8569320 | biostudies-literature
Project description:Terpinen-4-ol (TP4O) is the main component of the essential oil extracted from Melaleuca alternifolia, known as the tea tree, of the botanical family Myrtaceae. The anticancer effects of TP4O have been reported in several cancer cell lines. Previous reports have demonstrated that TP4O exerts anticancer effects by inducing apoptotic cell death in several cell lines; however, the underlying molecular mechanisms of these effects remain unclear. In the present study, the anticancer effects of TP4O against the colorectal cancer (CRC) cell lines HCT116 and RKO were evaluated using WST-8 and bromodeoxyuridine assays. The mechanism of cell death was investigated by the measurement of caspase-3/7, Annexin V and lactate dehydrogenase release. Reactive oxygen species (ROS) levels induced by TP4O were evaluated by electron spin resonance and quantitative measurement of dihydroethidium. Localization of the ROS derived from mitochondria was observed by confocal inverted microscopy. Protein levels of ROS scavengers were assessed by western blotting analysis. To confirm the role of ROS, cell viability was measured in the presence of antioxidant reagents. In an in vivo xenograft model of ICR-SCID mice implanted with HCT116 cells, 200 mg/kg TP4O was injected locally, and tumor growth was compared with that of the control. TP4O induced apoptotic cell death in HCT116 and RKO cells in a dose-dependent manner, and TP4O also increased the levels of ROS generated by mitochondria. TP4O-induced cell death was rescued by administration of antioxidant regents. In vivo, TP4O inhibited the proliferation of HCT116 xenografts compared with that of the control group. The results of the present study suggest that TP4O induces apoptosis in CRC cells through ROS generation. Furthermore, TP4O is potentially useful for the development of novel therapies against CRC.
| S-EPMC5530226 | biostudies-other
Project description:Terpinen-4-ol, a monoterpene component of the essential oils of several aromatic plants, exhibits antitumor effects. In this study, the antitumor effects of terpinen-4-ol and the cellular and molecular mechanisms responsible for it were evaluated and studied, respectively on human nonsmall cell lung cancer (NSCLC) cells. Our results indicated that terpinen-4-ol elicited a dose-dependent cytotoxic effect, as determined by MTT assay. Increased sub-G1 population and annexin-V binding, activation of caspases 9 and 3, cleavage of poly(ADPribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated involvement of the mitochondrial apoptotic pathway in terpinen-4-ol-treated A549 and CL1-0 cells. Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. Notably, terpinen-4-ol was able to increase p53 levels in A549 and CL1-0 cells. Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. Moreover, intratumoral administration of terpinen-4-ol significantly suppressed the growth of s.c. A549 xenografts by inducing apoptosis, as confirmed by TUNEL assay. Collectively, these data provide insight into the molecular mechanisms underlying terpinen-4-ol-induced apoptosis in NSCLC cells, rendering this compound a potential anticancer drug for NSCLC.
| S-EPMC3133878 | biostudies-literature
Project description:Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epigenetic transcriptional reprogramming. By integrating metabolomics and transcriptomics in a triple-negative human breast cancer cell line, we show that genetic and pharmacological down-regulation of CtBP2 strongly reduces cell proliferation by modulating the redox balance, nucleotide synthesis, ROS generation, and scavenging. Our data highlight the critical role of NADH in controlling the oncogene-dependent crosstalk between metabolism and the epigenetically mediated transcriptional program that sustains energetic and anabolic demands in cancer cells.
| S-EPMC8534001 | biostudies-literature