Convergent evolution of Enterobacteriaceae in epidemiological networks with high antimicrobial use

点击翻译按钮获取中文摘要

Disease-causing bacteria that are resistant to antimicrobials are a global health concern. While there are many research programs looking into the nature and spread of antimicrobial resistance (AMR), little is known about the evolutionary 'stepping stones' that precede the emergence of resistance. Understanding these could help with identifying early warning signs and targeting public health interventions. We will investigate the underlying evolutionary mechanisms that give rise to antimicrobial resistance in bacteria. Unlike other studies, that are done solely in the laboratory, our novel approach will do this using a unique, real-world situation of bacterial populations transmitting among a high antimicrobial use community. We will focus on enteric bacteria, which cause diarrhoeal disease and are pathogens with the most worrying AMR. We will study bacterial genome sequences from real infections and identify genetic changes that happen alongside the development of AMR using the latest bioinformatic methods. We will then analyse hundreds of bacterial strains in the laboratory looking at behaviours that might help the bacteria develop AMR and associate these behaviours with our genetic changes, developing models to quantify which of these signatures is most important. Finally, we will confirm that these genetic changes contribute to the development of AMR by evolving bacteria with and without the genetic change in the presence of antimicrobials. This work will increase our knowledge of the critical problem of AMR by identifying genetic changes underlying the emergence of AMR in an important bacterial group. Because we are finding the genetic changes in a real-world setting and testing our hypotheses across hundreds of different bacterial strains, we know our findings will be important and could help us prevent AMR emergence by, for example, helping design new laboratory testing for use in AMR surveillance.