Probing the physiological role and mechanism of DedA proteins, an integral membrane protein family critical to viability and antimicrobial resistance

探究 DedA 蛋白的生理作用和机制，DedA 蛋白是一个对活力和抗菌素耐药性至关重要的完整膜蛋白家族

• 批准号: 2119776
• 金额: --
• 依托单位: University of Kent
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2119776
• 关键词: Probing; physiological; role; mechanism; DedA

Antimicrobial resistance is a major global health concern. The DedA family are integral membrane proteins involved in resistance to several antimicrobials in clinically relevant pathogens, including Pseudomonas aeruginosa and Klebsiella pneumoniae. A DedA protein in K. pneumoniae was recently shown to be essential for resistance to colistin, a drug of last resort used in the treatment of multidrug-resistant bacterial infections. In addition, there is emerging evidence that DedA proteins are essential for bacterial viability. Therefore, inhibiting the function of DedA proteins could sensitise bacteria to currently available antibiotics and may also provide the basis for new antibiotic development. However, the development of DedA inhibitors is beleaguered by our lack of understanding of DedA structure and mechanism or even a clear idea of their role in AMR and bacterial physiology. The goal of this multidisciplinary and collaborative project is to investigate the physiological role of DedA proteins using an array of microbiological approaches, and use protein biochemistry and biophysical methods to probe the structure and functional activity of DedA proteins in vitro.

抗微生物药物耐药性是一个主要的全球卫生问题。DedA家族是一种完整的膜蛋白，参与临床相关病原体（包括铜绿假单胞菌和肺炎克雷伯菌）对几种抗菌素的耐药性。肺炎克雷伯菌中的一种DedA蛋白最近被证明对粘菌素（一种用于治疗多重耐药细菌感染的最后手段）的耐药性至关重要。此外，越来越多的证据表明，DedA蛋白对细菌的生存能力至关重要。因此，抑制DedA蛋白的功能可以提高细菌对现有抗生素的敏感性，也可能为开发新的抗生素提供基础。然而，由于缺乏对DedA结构和机制的了解，甚至缺乏对其在AMR和细菌生理中的作用的明确认识，DedA抑制剂的开发受到了困扰。该多学科合作项目的目标是利用一系列微生物学方法研究DedA蛋白的生理作用，并利用蛋白质生物化学和生物物理方法在体外探测DedA蛋白的结构和功能活性。