Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Antibacterial Activities and Action Mode of Anti-hyperlipidemic Lomitapide Against Staphylococcus aureus_1

ABSTRACT: Lomitapide has been approved by FDA for years in reducing levels of low-density lipoprotein (LDL) in cases of familial hypercholesterolemia, whereas the antibacterial effect of lomitapide remains elusive. In this study, the inhibitory activities of lomitapide against Staphylococcus aureus, including both methicillin sensitive and resistant S. aureus, were first time discovered by drug repositioning. Lomitapide has shown the inhibitory activities not only on the planktonic cell growth but also on the biofilm formation of S. aureus. Moreover, lomitapide has shown mild bactericidal effect on planktonic cells of clinical S. aureus strains as indicated in time killing assay. In order to investigate the mechanism of actions of lomitapide, quantitative proteomics analysis was then applied and suggested that the pathways involved in the cell wall biosynthesis and protein biosynthesis might participate in its action mode, whereas the clinical applications of lomitapide antibacterial activities need to be extensive investigated.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Yuxi Zhao

LAB HEAD: Yuxi Zhao

PROVIDER: PXD031706 | Pride | 2022-03-29

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20210831-1-2MC-1.mzML	Mzml
	20210831-1-2MC-1.mzid.gz	Mzid
	20210831-1-2MC-1.raw	Raw
	20210831-1-2MC-2.raw	Raw
	20210831-1-2MC-3.raw	Raw

Items per page:

1 - 5 of 9

Similar Datasets

Phenotype and expression profile analysis of Staphylococcus aureus biofilms and planktonic cells in response to Licochalcone A

Project description:Staphylococcus aureus (S. aureus) is one of the most important pathogens in humans and animals. The formation of S. aureus biofilm is considered an important mechanism of antimicrobial resistance. Therefore, finding effective drugs against the biofilm produced by S. aureus has been a high priority. Licochalcone A, a natural plant product, was reported to have antibacterial activities and showed good activity against all 21 tested strains of S. aureus biofilm and planktonic cells. To detect the possible molecular mechanism of Licochalcone A against S. aureus biofillm or planktonic cells, Affymetrix GeneChips were used to determine the global comparative transcription of S. aureus biofilm and planktonic cells triggered by treatment with sub-bactericidal and sub-inhibitory concentrations of Licochalcone A, respectively. Staphylococcus aureus planktonic cells and biofilm were exposed for 60 minutes to Licochalcone A at concentration of 2 M-NM-<g/ml (1/2M-CM-^W MIC) and 64 M-NM-<g/ml (4M-CM-^W MIBC), respectively. 4 samples including 4 control samples are analyzed.

2014-07-01 | E-GEOD-58938 | biostudies-arrayexpress

Phenotype and expression profile analysis of Staphylococcus aureus biofilms and planktonic cells in response to Licochalcone A

2014-07-01 | GSE58938 | GEO

Gene expression profile analysis of Staphylococcus aureus treated with nisin

Project description:Staphylococcus aureus (S. aureus) has already to be one of the most commonly identified bacteria that cause food poisoning. S. aureus colonization in humans can cause serious infections, toxinoses and life threatening diseases. The bacteriocin nisin has been extensively used as potential natural preservative in the food industry, but the overall transcriptional response mechanisms of S. aureus to nisin are still poorly understood. To detect the possible molecular mechanism of nisin against S. aureus, Affymetrix GeneChips were used to determine the global comparative transcription of S. aureus cells triggered by treatment with sub-inhibitory concentrations of nisin. Staphylococcus aureus planktonic cells were exposed for 60 minutes to nisin at concentration of 4 M-NM-<g/ml (1/2M-CM-^W MIC). 2 samples including 2 control samples are analyzed.

2015-02-10 | E-GEOD-65750 | biostudies-arrayexpress

Enoxacin_ColonCancer

Project description:We show that the small molecule enoxacin, a fluroquinolone used as an antibacterial compound, enhances the production of miRNAs with tumor suppressor functions by its binding to the microRNA biosynthesis protein TRBP. The use of enoxacin in human cell cultures and xenografted, orthotopic and metastases mice models demonstrate a TRBP-dependent and cancer-specific growth inhibitory effect of the drug.

2011-09-24 | E-TABM-1077 | biostudies-arrayexpress

Symmetric Bis-benzimidazoles Are Potent Anti-Staphylococcal Agents with Dual Inhibitory Mechanisms against DNA Gyrase

Project description:Various bis-benzimidazole derivatives have been reported to possess activity against Gram-positive pathogens. No mechanism of action has been elucidated to fully account for the antibacterial activity of this class of compounds. A group of symmetric bis-benzimidazoles (BBZ) designed as anticancer agents have previously been shown to possess moderate antiproliferative activity. We sought to assess the antibacterial activity and mechanism of action of BBZ compounds against Staphylococcus aureus. Antibacterial activities were assessed by determination of minimal inhibitory concentrations (MICs), time-kill curves, and scanning electron microscopy. Transcriptional responses to BBZ treatment were determined using whole genome microarrays. Activities against bacterial type II topoisomerases were investigated using in vitro supercoiling, decatenation, DNA binding, and DNA cleavage inhibition assays. MICs for EMRSA-16 were between 0.03 and 0.5 μg/mL. The compounds showed concentration-dependent bactericidal activity and induced cell swelling and lysis. Transcriptional responses to BBZ were consistent with topoisomerase inhibition and DNA damage. A subset of BBZ compounds inhibited S. aureus DNA gyrase supercoiling activity with IC50 values in the range of 5−10 μM. This inhibition was subsequently shown to operate through both inhibition of binding of DNA gyrase to DNA and accumulation of single-stranded DNA breaks. We conclude that BBZ compounds are potent antistaphylococcal agents and operate at least in part through DNA gyrase inhibition, leading to the accumulation of single-stranded DNA breaks, and by preventing the binding of gyrase to DNA. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-106]

2012-10-14 | E-BUGS-106 | biostudies-arrayexpress

Molecular Docking and Proteomics Reveals the Synergistic Antibacterial Mechanism of Theaflavin with β-lactam Antibiotics Against MRSA

Project description:Recurrent epidemics of methicillin-resistant Staphylococcus aureus (MRSA) have illustrated that the effectiveness of antibiotics in clinical application is rapidly fading. A feasible approach is to combine natural products with existing antibiotics to achieve an antibacterial effect. In this molecular docking study, we found that theaflavin (TF) preferentially binds the allosteric site of penicillin-binding protein 2a (PBP2a), inducing the PBP2a active site to open, which is convenient for β-lactam antibiotics to treat MRSA infection, instead of directly exerting antibacterial activity at the active site. Subsequent TMT-labeled proteomics analysis showed that TF treatment did not significantly change the landscape of the Staphylococcus aureus (S. aureus) USA300 proteome.Checkerboard dilution tests and kill curve assays were performed to validate the synergistic effect of TF and ceftiofur, and the fractional inhibitory concentration index (FICI) was 0.1875.Our findings provide a potential therapeutic strategy to combine existing antibiotics with natural products to resolve the prevalent infections of multidrug-resistant pathogens.

2022-11-09 | PXD037668 | Pride

Repurposing cinacalcet suppresses multi-drug resistant Staphylococcus aureus by disruption of cell membrane and inhibits biofilm by targeting IcaR

Project description:Multi-drug resistant Staphylococcus aureus (S. aureus) infections continously threaten public health. The rapid escalation in morbidity and mortality rates associated with methicillin-resistant S. aureus (MRSA) infections necessitates the urgent development of novel antimicrobial agents. Our study reveals that the FDA-approved drug cinacalcet (CNA) effectively functions as an antibacterial and anti-biofilm agent against S. aureus without detectable resistance. It evidently improved survival rate of mice infected with clinical multi-resistant S. aureus in a pneumonia model. Subsequent proteomic and biochemical experiments suggest that the primary antibacterial mechanism involves membrane structure disruption, ATP content reduction, and reactive oxygen species (ROS) production. Concurrently, LiP-SMap combined with biochemical validation indicates that CNA inhibits biofilm formation by targeting IcaR, a negative regulator of icaADBC, thereby enhancing its binding capacity to the ica operator DNA and subsequently suppressing extracellular polysaccharide formation. Importantly, compared to vancomycin, CNA demonstrates stronger biofilm bacterial clearance in a mouse thigh infection model. Collectively, our findings propose that CNA can be repurposed as a potential therapeutic agent for treating multidrug-resistant S. aureus infections and their associated biofilms.

2024-02-07 | PXD041266 | Pride

MULTI-TARGETED FLAVONOID INHIBITION OF THE PATHOGENIC BACTERIUM STAPHYLOCOCCUS AUREUS: A Proteomic Characterization

Project description:Growth inhibition of the pathogen Staphylococcus aureus with currently available antibiotics is problematic in part due to bacterial biofilm protection. While Although the recently characterized natural products, including 3´,4´,5-trihydroxy-6,7-dimethoxy-flavone [1], 3´,4´,5,6,7-pentahydroxy-flavone [2] and 5-hydroxy-4´,7-dimethoxy-flavone [3] exhibit both antibiotic and biofilm inhibitory activities, the mode of action of such hydroxylated flavonoids with respect to S. aureus inhibition has is yet to be characterized. Enzymatic digestion and high- resolution MS mass spectral analysis of differentially expressed proteins from S. aureus, with and without exposure to antibiotic flavonoids (1-3) has allowed for the characterization of global -protein alterations induced by metabolite treatment. A total of 56, 92, and 110 proteins are were differentially expressed with bacterial exposure to 1, 2 or 3, respectively. Connectivity of identified proteins is characterized using a search tool for the retrieval of interacting genes/proteins (STRING) with multi-targeted S. aureus inhibition of energy metabolism and biosynthesis by the assayed flavonoids observed. Identifying the mode of action of natural products as antibacterial agents is expected to provide insight into the potential use of flavonoids alone or in combination with known therapeutic agents to effectively control S. aureus infection.

2017-05-30 | PXD006030 | Pride

Phenotype and RNA-Seq-Based Transcriptome Profiling of Staphylococcus aureus biofilms in response to Tea tree oil

Project description:RNA sequencing (RNA-Seq) was used in our study to elucidate the mechanism of Tea tree oil (TTO) as a potential antibacterial agent to evaluate differentially expressed genes and functional network analysis in S. aureus ATCC 29213 biofilms. Staphylococcus aureus biofilm cells were exposed for 60 minutes to TTO at concentration of 1/2ÃMBIC (1 mg/ml).2 samples including 2 control samples are analyzed.

2016-08-19 | E-GEOD-85787 | biostudies-arrayexpress

Repurposing Etalocib suppresses multidrug-resistant staphylococcus aureus

Project description:Staphylococcus aureus (S. aureus) is common gram-positive bacteria that prominently causes community acquired infection (CAI) and hospital acquired infection (HAI) makes it a versatile and dangerous, Antibiotic resistance and the long - term nature of new drug research and development have forced the search for new research methods of antibacterial drugs. Drug repositioning is a new research approach for antibacterial drugs. Etalocib is found through screening the compound library, and its antibacterial activity is studied and the antibacterial mechanism is explored.

2024-11-11 | PXD057734 |

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data