1. Identification of bacterial genes involved in antibiotic resistance using whole genome screens

1. 使用全基因组筛选鉴定与抗生素耐药性相关的细菌基因

• 批准号: G1100100/1
• 负责人: Julian Parkhill
• 金额: $ 90.17万
• 依托单位: Wellcome Sanger Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1100100%2F1
• 关键词: 1.; Identification; bacterial; genes; involved

Antibiotic resistance in disease-causing bacteria has spread, resulting in the inability to treat some bacterial infections, which can lead to the deaths of patients. Bacteria can become resistant to antibiotics using different mechanisms, only some of which have been characterised. A better understanding of how bacteria resist antibiotic action will assist in the making of new antibiotics, may provide new ways of controlling resistance, and help us to predict when resistance to a particular antibiotic is likely to arise, allowing a pre-emptive switch to a different antibiotic for disease treatment. At the Sanger Institute, by using the latest DNA sequencing technology to analyse very large collections of bacterial mutants, we can firstly identify those components of the bacterial cell that are essential for life. These provide candidate targets for the development of new antibiotics. Secondly, we can measure every non-essential component of the bacterial cell for its contribution to antibiotic resistance. We have performed a pilot study which has shown that the method also tells us which cellular components contribute to the bacterial cells? sensitivity to antibiotics. This information tells us how it may, in the future, be possible to make resistant bacteria susceptible once again to antibiotics. It also gives us a more complete understanding of how bacteria resist antibiotics, and in general provides clues as to the role of the bacterial cell components, as the role of most components is not fully understood and the role of many is unknown. It is proposed to perform these experiments on a number of disease causing bacteria: the large mutant collections needed are already available for Salmonella Typhi which causes typhoid fever, and Salmonella Typhimurium which causes food poisoning. In addition, mutant collections will be made in MRSA (a strain of Staphylococcus aureus), Enterobacter cloacae, and E. coli, all of which cause infections acquired by patients whilst in hospital, and are particularly dangerous for individuals who are already ill with other medical conditions. Many antibiotics exist, but there are relatively few different types. Using one of each type will maximise our understanding of antibiotic resistance mechanisms for significantly less effort and expense. Once the data have been generated, they will be made available, in an easy to understand form, on the Sanger Institute web site where they will provide a freely and widely available resource for researchers and any other interested parties.

致病细菌的抗生素耐药性已经蔓延，导致无法治疗某些细菌感染，这可能导致患者死亡。细菌可以通过不同的机制对抗生素产生耐药性，其中只有一些机制已经被描述。更好地了解细菌如何抵抗抗生素作用将有助于制造新的抗生素，可能提供控制耐药性的新方法，并帮助我们预测何时可能出现对特定抗生素的耐药性，从而允许先发制人地转换为不同的抗生素用于疾病治疗。在桑格研究所，通过使用最新的DNA测序技术来分析大量的细菌突变体，我们可以首先识别出细菌细胞中对生命至关重要的成分。这些为新抗生素的开发提供了候选靶点。其次，我们可以测量细菌细胞的每个非必需成分对抗生素耐药性的贡献。我们进行了一项初步研究，结果表明该方法还告诉我们哪些细胞成分对细菌细胞有贡献？对抗生素敏感。这些信息告诉我们，将来如何可能使耐药细菌再次对抗生素敏感。它还使我们更全面地了解细菌如何抵抗抗生素，并在一般情况下提供了细菌细胞成分的作用的线索，因为大多数成分的作用尚未完全了解，许多成分的作用是未知的。建议对许多致病细菌进行这些实验：所需的大量突变体收集已经可用于引起伤寒的伤寒沙门氏菌和引起食物中毒的鼠伤寒沙门氏菌。此外，将在MRSA（金黄色葡萄球菌的一种菌株）、阴沟肠杆菌和大肠杆菌中进行突变体收集。大肠杆菌，所有这些都会导致病人在住院期间感染，对已经患有其他疾病的人来说特别危险。有许多抗生素存在，但有相对较少的不同类型。使用每种类型中的一种将最大限度地提高我们对抗生素耐药性机制的理解，从而大大减少工作量和费用。一旦数据生成，将以易于理解的形式在桑格研究所网站上提供，研究人员和任何其他感兴趣的各方将在网站上免费和广泛地获得这些数据。