Understanding multiple antibiotic resistance in Gram-negative bacteria

了解革兰氏阴性菌的多重抗生素耐药性

• 批准号: BB/N014200/1
• 负责人: David Grainger
• 金额: $ 47.24万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN014200%2F1
• 关键词: Understanding; multiple; antibiotic; resistance; Gram

Antibiotics underpin modern medical, veterinary and farming practices worldwide. However, the efficacy of antibiotics is decreasing. A simple genetic system called mar, which can provide protection against multiple antibiotics, will be the focus of our project. Briefly, mutations in this system result in triggering of bacterial defences. Consequently, the bacterial cell is able to protect itself from many different toxic agents. We seek to identify and understand all of the cellular pathways that link this defence system to antibiotic resistance. By understanding pathways to drug resistance, we will provide new opportunities to control bacterial infections. Importantly, the pathways we will investigate are similar in many microbes. As a result, our findings will be applicable to many bacterial infections and so of broad interest.Antibiotics are often used with no knowledge of the infecting microorganism. Hence, widespread use of antibiotics favours the emergence of antibiotic resistant bacteria. Our experiments will be done using a bacterium called E. coli. This organism is commonly found in people and animals, including pigs. Furthermore, pigs are among the most common recipients of antibiotics in the EU and the number of serious E. coli infections in people is increasing. Indeed, the type of E. coli we will investigate has acquired mutations in the defence system we will study. Therefore, we will address a major health issue relevant to the UK animal food production industry as well as animal and human health. Importantly, this application comes at a time when there are global calls for a better understanding of antibiotic resistance.

抗生素是全球现代医疗、兽医和农业实践的基础。然而，抗生素的疗效正在下降。一个简单的遗传系统称为mar，它可以提供对多种抗生素的保护，将是我们项目的重点。简言之，该系统中的突变导致细菌防御的触发。因此，细菌细胞能够保护自己免受许多不同的有毒物质的侵害。我们试图识别和理解将这种防御系统与抗生素耐药性联系起来的所有细胞途径。通过了解耐药性的途径，我们将为控制细菌感染提供新的机会。重要的是，我们将研究的途径在许多微生物中是相似的。因此，我们的发现将适用于许多细菌感染，因此具有广泛的意义。抗生素通常在不了解感染微生物的情况下使用。因此，抗生素的广泛使用有利于抗生素耐药性细菌的出现。我们的实验将使用一种叫做E.杆菌这种微生物常见于人和动物，包括猪。此外，猪是欧盟最常见的抗生素接受者之一，严重的E。大肠杆菌感染的人数正在增加。实际上，E.我们将研究的大肠杆菌在我们将研究的防御系统中获得了突变。因此，我们将解决与英国动物食品生产行业以及动物和人类健康相关的重大健康问题。重要的是，这一应用是在全球呼吁更好地了解抗生素耐药性的时候出现的。

项目成果

The multiple antibiotic resistance operon of enteric bacteria controls DNA repair and outer membrane integrity.

• DOI: 10.1038/s41467-017-01405-7
• 发表时间: 2017-11-13
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Sharma P;Haycocks JRJ;Middlemiss AD;Kettles RA;Sellars LE;Ricci V;Piddock LJV;Grainger DC
• 通讯作者: Grainger DC