Staphylococcus aureus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA721282 | ENA |
REPOSITORIES: ENA
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Project description:To establish general differences between the protein expression in S. aureus strains, five methicillin sensitive S. aureus (MSSA) strains and five methicillin resistant S. aureus (MRSA) strains were compared both individually and as MSSA and MRSA groups in the absence of antibiotics. Proteins were compared by ultra-performance liquid chromatography-mass spectrometry.
2023-04-25 | PXD021629 | Pride
Project description:Subinhibitory concentrations of the neuroleptic drug thioridazine (TDZ) are well-known to enhance the killing of methicillin-resistant S. aureus (MRSA) by β-lactam antibiotics, however, the mechanism underlying the synergy between TDZ and β-lactams is not fully understood. In the present study we have examined the effect of a subinhibitory concentration of TDZ on antimicrobial resistance, the global transcriptome, and the cell wall composition of MRSA USA300. We show that TDZ is able to sensitize the bacteria to several classes of antimicrobials targeting the late stages of peptidoglycan synthesis. Furthermore, our microarray analysis demonstrates that TDZ modulates the expression of genes encoding membrane and surface proteins, transporters, and enzymes involved in amino acid biosynthesis. Interestingly, resemblance between the transcriptional profile of TDZ treatment and the transcriptomic response of S. aureus to known inhibitors of cell wall synthesis suggests that TDZ disturbs peptidoglycan biosynthesis at a stage that precedes transpeptidation. In support of this notion, dramatic changes in the muropeptide profile of USA300 were observed following growth in the presence of TDZ, indicating that TDZ can interfere with the formation of the pentaglycine branches. Strikingly, the addition of glycine to the growth medium relieved the effect of TDZ on the muropeptide profile. Furthermore, exogenous glycine offered a modest protective effect against TDZ-induced β-lactam sensitivity. We propose that TDZ exposure leads to a shortage of intracellular amino acids, including glycine, which is required for the production of normal peptidoglycan precursors with pentaglycine branches, the correct substrate of S. aureus penicillin-binding proteins. Collectively, this work demonstrates that TDZ has a major impact on the cell wall biosynthesis pathway in S. aureus and provides new insights into how MRSA may be sensitized towards β-lactam antibiotics.
2013-05-20 | GSE43759 | GEO
Project description:Methicillin resistant S.aureus (MRSA) resistance to beta-lactam is dependent on environmental conditions. In physiologically relevant conditions present in RPMI (supplemented with 10% LB for proper growth) the MIC of beta lactam Nafcillin drops more than 20 fold when compared to MIC in bateriological Cation Adjusted Mueller Hinton Broth(CAMHB). In order to elucidate the underlying mechanism behind this difference, MRSA isolate TCH1516 was grown in each media in presence of varying levels of nafcillin. At 2.5 hour timepoint cells were harvested and expression profile determined with RNA sequencing.
2018-06-05 | GSE115309 | GEO
Project description:Bactericidal antibiotics are powerful drugs because they not only inhibit essential bacterial functions, but convert them into toxic processes. Many bacteria are remarkably tolerant against antibiotics, due to inducible damage repair responses. How these responses promote whole population tolerance in important human pathogens is poorly understood. The two-component system VxrAB of the diarrheal pathogen Vibrio cholerae, a model system for tolerance against cell wall damaging (e.g., beta-lactam) antibiotics, is required for high-level beta-lactam tolerance. Here, we report the mechanism of VxrAB-mediated survival. We find that -lactam antibiotics inappropriately induce the Fur-regulated iron starvation response, causing an increase in intracellular free iron and colateral oxidative damage. VxrAB reduces antibiotic-induced toxic influx of Fe by downregulating iron importers and induces cell wall synthesis functions to counteract cell wall damage. Our results highlight the complex responses elicited by antibiotics and suggest that the ability to counteract diverse stresses promotes high-level antibiotic tolerance.
2019-07-30 | GSE135009 | GEO
Project description:Bactericidal antibiotics are powerful drugs because they not only inhibit essential bacterial functions, but convert them into toxic processes. Many bacteria are remarkably tolerant against antibiotics, due to inducible damage repair responses. How these responses promote whole population tolerance in important human pathogens is poorly understood. The two-component system VxrAB of the diarrheal pathogen Vibrio cholerae, a model system for tolerance against cell wall damaging (e.g., beta-lactam) antibiotics, is required for high-level beta-lactam tolerance. Here, we report the mechanism of VxrAB-mediated survival. We find that -lactam antibiotics inappropriately induce the Fur-regulated iron starvation response, causing an increase in intracellular free iron and colateral oxidative damage. VxrAB reduces antibiotic-induced toxic influx of Fe by downregulating iron importers and induces cell wall synthesis functions to counteract cell wall damage. Our results highlight the complex responses elicited by antibiotics and suggest that the ability to counteract diverse stresses promotes high-level antibiotic tolerance.
2019-07-30 | GSE135010 | GEO
Project description:Purpose: Staphylococcus aureus is a highly successful human pathogen responsible for wide range of infections. In this study, we provide insights into the virulence, pathogenicity, and antimicrobial resistance determinants of methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA; MRSA) recovered from non-healthcare environments. Experiment design: Three environmental MSSA and three environmental MRSA were selected for proteomic profiling using iTRAQ MS/MS. Gene Ontology (GO) Annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Annotation were applied to interpret the functions of the proteins detected. Results: 792 proteins were identified in MSSA and MRSA. Comparative analysis of MRSA and MSSA revealed that 8 of out 792 proteins were up-regulated and 156 down-regulated. Differentially abundant proteins were predominantly involved in catalytic and binding activity. Among 164 proteins that had differences in abundance, 29 proteins were involved in pathogenesis, antimicrobial activities，stress response, mismatch repair and cell wall synthesis. Twenty-two proteins associated with pathogenicity, including spa, sbi, clfA and dlt were up-regulated in MRSA. Moreover, the up-regulated pathogenic protein entC2 in MSSA was determined to be a super antigen potentially capable of triggering toxic shock syndrome in the host. Conclusions: Enhanced pathogenicity, antimicrobial activity and stress response were observed in MRSA compared to MSSA.
2020-01-09 | PXD014478 | Pride
Project description:Mycobacterium abscessus (Mab) causes serious infections that often require over 18 months of antibiotic combination therapy. With β lactam antibiotics being safe, double β-lactam and β-lactam/β-lactamase inhibitor combinations are of interest for improving treatment of Mab infections and minimizing toxicity. However, a mechanistic approach for building these combinations is lacking since little is known about which penicillin-binding protein (PBP) target receptors are inactivated by different β-lactams in Mab. This project aimed to identify PBPs in Mab and study the binding affinities of each of these PBPs with β-lactam antibiotics. These first PBP occupancy patterns in Mab provide a mechanistic foundation for selecting and optimizing safe and effective combination therapies with β-lactams.
2020-11-24 | PXD022644 | Pride
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen in both community and health care settings, which causes a wide range of infections. Its resistance to β-lactam antibiotics and methicillin in particular, greatly complicates treatment options and success rate due to the limited number of antibiotics with activity against MRSA. To further the development of alternative therapeutics, the mechanisms that mediate antibiotic resistance in MRSA need to be fully understood. Cannabinoid compounds including cannabidiol (CBD), tetrahydrocannabinol (THC) and cannabinol (CBN) have shown promise as potential antibiotic adjuvants. In the present study, MRSA cells were subjected to antibiotic stress from methicillin in combination with three cannabinoid compounds, and subsequently analysed using metaproteomics to assess the metabolic response. Subjecting MRSA to methicillin made the cells more viable and increased their energy production, as well as upregulation of penicillin-binding protein 2 (PBP2). The cannabinoids all showed antimicrobial activity against MRSA, and inhibited the energy production of the cells as well as PBP2 when used in combination with methicillin. Furthermore, all three cannabinoid compounds inhibited resistance mechanisms in MRSA, resulting in a decrease in the minimum inhibitory concentration (MIC) of methicillin when used in combination.
2022-01-18 | PXD024244 | Pride
Project description:Lignin is an aromatic plant cell wall polymer that facilitates water transport through the vasculature of plants. Although lignin’s ability to reduce bacterial growth been previously reported, it’s hydrophobicity complicates the ability to examine its biological effects on living cells in aqueous growth media. We recently described the ability to solvate lignin in Good’s buffers with neutral pH, a breakthrough that has allowed examination of lignin’s antimicrobial effects against the human pathogen Staphylococcus aureus. We previously showed that lignin damages the S. aureus cell membrane, causes increased cell clustering, and inhibits growth synergistically with tunicamycin, a teichoic acid synthesis inhibitor. In this current study, additional experiments were performed to better understand the physiological and transcriptomic responses of S. aureus to lignin. Intriguingly, lignin restored the susceptibility of genetically resistant S. aureus isolates to β-lactam antibiotics, dysregulated intracellular pH, and impaired normal cell division. Additionally, RNAseq analysis of lignin-treated cultures revealed a number of gene expression changes related to cell envelope, cell wall physiology, fatty acid metabolism and stress resistance. Altogether, these results represent the first comprehensive analysis of lignin’s antibacterial activity against S. aureus that provide clarity in deciphering the mechanisms of lignin’s antibacterial activity, while supporting the notion that lignin has potential to be repurposed for biomedical applications.
2022-07-12 | GSE198912 | GEO
Project description:Subinhibitory concentrations of the neuroleptic drug thioridazine (TDZ) are well-known to enhance the killing of methicillin-resistant S. aureus (MRSA) by β-lactam antibiotics, however, the mechanism underlying the synergy between TDZ and β-lactams is not fully understood. In the present study we have examined the effect of a subinhibitory concentration of TDZ on antimicrobial resistance, the global transcriptome, and the cell wall composition of MRSA USA300. We show that TDZ is able to sensitize the bacteria to several classes of antimicrobials targeting the late stages of peptidoglycan synthesis. Furthermore, our microarray analysis demonstrates that TDZ modulates the expression of genes encoding membrane and surface proteins, transporters, and enzymes involved in amino acid biosynthesis. Interestingly, resemblance between the transcriptional profile of TDZ treatment and the transcriptomic response of S. aureus to known inhibitors of cell wall synthesis suggests that TDZ disturbs peptidoglycan biosynthesis at a stage that precedes transpeptidation. In support of this notion, dramatic changes in the muropeptide profile of USA300 were observed following growth in the presence of TDZ, indicating that TDZ can interfere with the formation of the pentaglycine branches. Strikingly, the addition of glycine to the growth medium relieved the effect of TDZ on the muropeptide profile. Furthermore, exogenous glycine offered a modest protective effect against TDZ-induced β-lactam sensitivity. We propose that TDZ exposure leads to a shortage of intracellular amino acids, including glycine, which is required for the production of normal peptidoglycan precursors with pentaglycine branches, the correct substrate of S. aureus penicillin-binding proteins. Collectively, this work demonstrates that TDZ has a major impact on the cell wall biosynthesis pathway in S. aureus and provides new insights into how MRSA may be sensitized towards β-lactam antibiotics. Staphylococcus aureus USA300 was grown to early exponential phase and treated with TDZ (16 µg/ml) alone or in combination with DCX (0.125 µg/ml) for 30 min. Changes in global gene expression were analyzed using the untreated culture as control. Hybridizations were performed in triplicate using RNA isolated from independent cultures.
2013-05-20 | E-GEOD-43759 | biostudies-arrayexpress