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

点击翻译按钮获取中文摘要

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.