Probiotic Enterococcus mundtii H81 Inhibits the NF-κb Signaling Pathway to Ameliorate Staphylococcus Aureus-Induced Mastitis in Mice

2021 ◽  
Author(s):  
Min Qiu ◽  
Lianjun Feng ◽  
Xiaoyu Hu ◽  
Siyuan Gao ◽  
Caijun Zhao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Signaling Pathway ◽  
Enterococcus Mundtii

scholarly journals Exploration of Anti-Staphylococcus Aureus Activity and Molecular Mechanism of Wuweixiaoduyin using Network Pharmacology Anti-Staphylococcus Aureus Activity of Wuweixiaoduyin using Network Pharmacology

2021 ◽  
Author(s):  
Kai Huang ◽  
Bigyuan Lin ◽  
Haiyong Ren ◽  
Qifen Mao ◽  
Qiaofeng Guo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Target Genes ◽  
Therapeutic Targets ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Pathway Enrichment ◽  
Aureus Infection

Abstract Background:S. aureus (Staphylococcus aureus) infection imposes a serious burden to global healthcare systems. WWXDY (Wuweixiaoduyin) is a traditional Chinese medicine, and it is usually used to treat infections in China. This study aimed to explore the active compounds, therapeutic targets, key pathways, and potential mechanisms of WWXDY in the treatment of S. aureus infection. Materials & Methods:Data related to active compounds and therapeutic targets of WWXDY for treating S. aureus were collected from DisGeNET, GeneCards, and DrugBank databases. To explore the roles of the active targets in gene function and signaling pathways, KEGG (Kyoto Gene and Genomics Encyclopedia) pathway enrichment and GO (Gene Ontology) analyses of the 122 target genes in the PPI (protein-protein interaction) network were performed. We further performed NP (network pharmacology) by using a network analyzer to screen 30 key targets. Results:A total 92 active compounds of WWXDY were screened. The 122 overlapped genes were found from 785 therapeutic targets and 684 S. aureus-related genes. Besides, 92 active compounds of WWXDY, such as mandenol, ethyllinolenate, eriodyctiol, secologanic dibutylacetal_qt, etc., were identified. The PPI network of the effective ingredients of WWXDY in treating S. aureus infection identified the top 30 genes, including IL-6 (interleukin-6), TNF-α (tumor necrosis factor-α), VEGFA (vascular endothelial growth factor A), AKT1, CXCL8, MAPK3 (mitogen-activated protein kinase 3), TLR (toll-like receptor 4), IL-1β, EGFR (epidermal growth factor receptor), and MMP9 (matrix metalloproteinase-9). Conclusion:The GO functional and KEGG pathway enrichment analyses indicated that 122 overlapped genes were mainly enriched in COVID-19, AGE-RAGE signaling pathway, C-type lectin receptor signaling pathway, Pertussis, and Chagas disease. Our findings indicated the active compounds and therapeutic targets of WWXDY in treating S. aureus infection, as well as its potential mechanisms.

scholarly journals Expression Profiling of microRNA From Peripheral Blood of Dairy Cows in Response to Staphylococcus aureus-Infected Mastitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhuo-Ma Luoreng ◽  
Jian Yang ◽  
Xing-Ping Wang ◽  
Da-Wei Wei ◽  
Lin-Sen Zan
Keyword(s):  
Staphylococcus Aureus ◽  
Research And Development ◽  
Dairy Cows ◽  
Signaling Pathway ◽  
Dairy Cow ◽  
Peripheral Blood ◽  
Economic Benefits ◽  
Molecular Therapy ◽  
Receptor Interaction ◽  
Regulated Expression

As the main pathogen causing dairy cow mastitis, Staphylococcus aureus can cause subclinical mastitis, which is difficult to be diagnosed. It seriously affects milk quality and the economic benefits of the dairy industry. Therefore, it is very necessary to find biomarkers for early diagnosis of S. aureus-infected mastitis in peripheral blood of dairy cows. In this study, S. aureus was used to infect the mammary gland tissues of dairy cows, and a mastitis model was successfully constructed. The RNAseq technology was used to determine the expression profiles of microRNA (miRNA) from peripheral blood of dairy cows infected with S. aureus at 0, 1, 3, 5, and 7 days. A total of 288 differentially expressed miRNAs (DIE-miRNAs) were found, of which 108 were known miRNAs and 180 were novel predicted miRNAs. Bioinformatics analysis results showed that the above DIE-miRNAs might be involved in 10 immune system-related signaling pathways (i.e., chemokine signaling pathway, leukocyte transendothelial migration, natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathway, Jak-STAT signaling pathway, MAPK signaling pathway, Wnt signaling pathway, cell adhesion molecules, cytokine-cytokine receptor interaction, and ECM-receptor interaction), thus regulating the process of S. aureus mastitis. It was also found that the expression variation of up-regulated expression of miR-320a, miR-19a, and miR-19b as well as down-regulated expression of miR-143, miR-205, and miR-24 reached a significant level on the 5th and 7th day of infection, suggesting that they might play an important biological role in mastitis and provide a direction for the research and development of molecular therapy technology for mastitis. However, at different times after S. aureus infection, miR-1301 was significantly up-regulated in peripheral blood. miR-2284r was significantly down-regulated, suggesting that these two miRNAs might be the new blood biomarkers for S. aureus-infected dairy cow mastitis. The above results laid a new foundation for the research and development of molecular diagnosis and biological therapy technology for S. aureus-infected mastitis in dairy cow.

scholarly journals Staphylococcus aureus α-toxin-mediated cation entry depolarizes membrane potential and activates p38 MAP kinase in airway epithelial cells

2016 ◽  
Vol 311 (3) ◽  
pp. L676-L685 ◽  
Author(s):  
Ina Eiffler ◽  
Jane Behnke ◽  
Sabine Ziesemer ◽  
Christian Müller ◽  
Jan-Peter Hildebrandt
Keyword(s):  
Staphylococcus Aureus ◽  
Plasma Membrane ◽  
Membrane Potential ◽  
Epithelial Cells ◽  
Map Kinase ◽  
Signaling Pathway ◽  
Airway Epithelial Cells ◽  
P38 Map Kinase ◽  
Airway Epithelial ◽  
Transmembrane Pores

Membrane potential ( Vm)-, Na+-, or Ca2+-sensitive fluorescent dyes were used to analyze changes in Vm or intracellular ion concentrations in airway epithelial cells treated with Staphylococcus aureus α-toxin (Hla), a major virulence factor of pathogenic strains of these bacteria. Gramicidin, a channel-forming peptide causing membrane permeability to monovalent cations, a mutated form of Hla, rHla-H35L, which forms oligomers in the plasma membranes of eukaryotic cells but fails to form functional transmembrane pores, or the cyclodextrin-derivative IB201, a blocker of the Hla pore, were used to investigate the permeability of the pore. Na+ as well as Ca2+ ions were able to pass the Hla pore and accumulated in the cytosol. The pore-mediated influx of calcium ions was blocked by IB201. Treatment of cells with recombinant Hla resulted in plasma membrane depolarization as well as in increases in the phosphorylation levels of paxillin (signaling pathway mediating disruption of the actin cytoskeleton) and p38 MAP kinase (signaling pathway resulting in defensive actions). p38 MAP kinase phosphorylation, but not paxillin phosphorylation, was elicited by treatment of cells with gramicidin. Although treatment of cells with rHla-H35L resulted in the formation of membrane-associated heptamers, none of these cellular effects were observed in our experiments. This indicates that formation of functional Hla-transmembrane pores is required to induce the cell physiological changes mediated by α-toxin. Specifically, the changes in ion equilibria and plasma membrane potential are important activators of p38 MAP kinase, a signal transduction module involved in host cell defense.

scholarly journals TLR8 Senses Staphylococcus aureus RNA in Human Primary Monocytes and Macrophages and Induces IFN-β Production via a TAK1–IKKβ–IRF5 Signaling Pathway

2015 ◽  
Vol 195 (3) ◽  
pp. 1100-1111 ◽  
Author(s):  
Bjarte Bergstrøm ◽  
Marie H. Aune ◽  
Jane A. Awuh ◽  
June F. Kojen ◽  
Kjetil J. Blix ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Signaling Pathway ◽  
Monocytes And Macrophages

scholarly journals Acetylharpagide Protects Mice from Staphylococcus Aureus-Induced Acute Lung Injury by Inhibiting NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5523
Author(s):  
Zhaoxin Zhang ◽  
Yun Wang ◽  
Yating Shan ◽  
Wu Yin
Keyword(s):  
Staphylococcus Aureus ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Gas Barrier ◽  
Interacting Protein ◽  
Risk Of Death ◽  
Serious Disease

Staphylococcus aureus (S. aureus)-induced acute lung injury (ALI) is a serious disease that has a high risk of death among infants and teenagers. Acetylharpagide, a natural compound of Ajuga decumbens Thunb. (family Labiatae), has been found to have anti-tumor, anti-inflammatory and anti-viral effects. This study investigates the therapeutic effects of acetylharpagide on S. aureus-induced ALI in mice. Here, we found that acetylharpagide alleviated S. aureus-induced lung pathological morphology damage, protected the pulmonary blood-gas barrier and improved the survival of S. aureus-infected mice. Furthermore, S. aureus-induced myeloperoxidase (MPO) activity of lung homogenate and pro-inflammatory factors in bronchoalveolar lavage (BAL) fluid were suppressed by acetylharpagide. Mechanically, acetylharpagide inhibited the interaction between polyubiquitinated receptor interacting protein 1 (RIP1) and NF-κB essential modulator (NEMO), thereby suppressing NF-κB activity. In summary, these results show that acetylharpagide protects mice from S. aureus-induced ALI by suppressing the NF-κB signaling pathway. Acetylharpagide is expected to become a potential treatment for S. aureus-induced ALI.

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