与抗生素耐药性相关的Staphylococcus aureus传感器histidine kinase VraS突变影响了酶催化,稳定性和基质相互作用
Brittnee Cagle-White1, Shrijan Bhattarai1, Allison Sunderhaus1
1Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, TX, USA.
Archives of biochemistry and biophysics
|December 26, 2025
概括
黄金葡萄球菌的突变增强了它的活性和稳定性,有助于抗生素耐药性. 了解这些变化对于开发抗性黄金色杆菌感染的新疗法至关重要.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 黄金葡萄球菌使用VraSR系统进行细胞壁合成和抗生素耐药性.
- 在VraS中,单核酸多态性与电阻有关,但它们的功能影响尚不清楚.
研究的目的:
- 研究来自耐药菌株的七种VraS突变对其酶活性,稳定性和与VraR的结合亲和力的影响.
- 阐明这些突变在Staphylococcus aureus抗生素耐药性的作用.
主要方法:
- 优化野生类型和突变Vras蛋白的表达和净化.
- 利用合激酶试验来检测自酸化动力学.
- 在蛋白质稳定性评估中采用差分扫描度测量.
- 使用表面等离子体共振来测量VraS-VraR结合亲和力.
- 在VraS同质模型上进行分子动力学模拟.
主要成果:
- 几种VraS突变增加了催化效率和蛋白质稳定性.
- 大多数突变物对VraR保持了野生类型的亲和力,除了D242G,该突变物显示17倍的减少.
- 根据模拟,M192I突变可能会增强迈凯利斯复合体的形成.
结论:
- VraS突变显著改变了它的酶性质和稳定性,可能会影响细菌的应激反应.
- 研究细菌激酶突变对于理解和对抗S. aureus的抗生素耐药性至关重要.
相关概念视频
Gene Regulation in Microbial Communities: Quorum Sensing
457
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
457
Development of Antibiotic Resistance
1.1K
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
1.1K
Ligand Binding and Linkage
5.4K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.4K
Allosteric Proteins-ATCase
6.4K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.4K
Mismatch Repair
43.4K
Overview
43.4K
Antibiotic Selection
59.3K
Overview
59.3K


