关键词: antibiotic resistance arginine biosynthesis biofilm efflux membrane permeability nanosilver network analysis transcriptome

来  源:   DOI:10.3390/pharmaceutics16060726   PDF(Pubmed)

Abstract:
Antibiotic-resistant strains of Staphylococcus aureus are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial to the development of new effective antibacterial formulations. We investigated the antibacterial effect of a colloidal nanosilver formulation, Silversol®, against an antibiotic-resistant strain of S. aureus using appropriate in vitro assays. Moreover, we deciphered the molecular mechanisms underlying this formulation\'s anti-S. aureus activity using whole transcriptome analysis. Lower concentrations of the test formulation exerted a bacteriostatic effect against this pathogen, and higher concentrations exerted a bactericidal effect. Silversol® at sub-lethal concentration was found to disturb multiple physiological traits of S. aureus such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed that the genes coding for transcriptional regulators, efflux machinery, transferases, β-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis are expressed differently under the influence of the test formulation. Genes (argG and argH) involved in arginine biosynthesis emerged among the major targets of Silversol®\'s antibacterial activity against S. aureus.
摘要:
金黄色葡萄球菌的抗生素抗性菌株被各种公共卫生机构视为严重威胁。在这种重要的病原体中识别新的靶标对于开发新的有效抗菌制剂至关重要。我们研究了胶体纳米银制剂的抗菌作用,Silversol®,使用适当的体外试验对金黄色葡萄球菌的抗生素抗性菌株。此外,我们破译了该制剂抗S的分子机制。使用全转录组分析的金黄色葡萄球菌活性。较低浓度的测试制剂对这种病原体具有抑菌作用。较高的浓度会产生杀菌作用。发现亚致死浓度的Silversol®会干扰金黄色葡萄球菌的多种生理特性,例如生长,抗生素敏感性,膜渗透性,外排,蛋白质合成和出口,生物膜和胞外多糖的生产,等。转录组数据显示,编码转录调节因子的基因,外排机械,转移酶,β-内酰胺抗性,氧化还原酶,金属稳态,毒力因子,和精氨酸生物合成在测试制剂的影响下不同地表达。参与精氨酸生物合成的基因(argG和argH)出现在Silversol®抗金黄色葡萄球菌抗菌活性的主要靶标中。
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