Using population genomics to recognise and prevent the emergence and establishment of Klebsiella pneumoniae high-risk lineages

该项目将重点放在英国、阿根廷和马拉维三个不同地区的三个纵向肺炎克雷伯菌样本的比较种群基因组学上，这些样本跨越12-20年。目前关于肺炎克雷伯菌的数据几乎完全基于对特定病房/医院的短期研究，通常是在非常不同的环境中。这使得无法分析长期信号，因为这需要比较高度混淆的数据，例如来自不同国家的分离物代表的不同年份，从而无法区分隔离时间和隔离国的影响。三种高度不同的设置的比较减少了这一混杂因素，因为患者接待组随着时间的推移保持相似。为了自信地识别全球适用的普遍有效的信号，这个项目将比较在三个不同环境中触发谱系扩张的因素。然后，可以将在相关环境中观察到的种群的时间变化相互比较，以确定当所有人都具有相似的AMR决定因素时，是什么使肺炎克雷伯菌谱系比其他谱系成功的共同规则。了解是什么导致了新的高危基因谱系的出现，对于形成高危克隆出现的早期预警系统，并将感染控制的努力集中在这些方面，特别是在资源有限的情况下，至关重要。

This project will focus on comparative population genomics of three longitudinal collections of K. pneumoniae spanning 12-20 years from three diverse settings; the UK, Argentina and Malawi. Current data on K. pneumoniae is almost exclusively based on short-term studies of specific wards/hospitals, often in highly different settings. This makes the analysis of long-term signals impossible, as this would require the comparison of highly confounded data, e.g. different years represented by isolates from different countries, making it impossible to distinguish between the influence of time of isolation from the country of isolation. The comparison of three highly different settings reduces this confounder, as the patient catchment group remains similar over time. To confidently recognise globally applicable signals that are universally valid, this project will compare what triggers lineage expansion in the three different settings with each other. The observed temporal changes in the population in the relevant settings can then be compared with each other, to identify shared rules for what makes a K. pneumoniae lineage successful over others when all share similar AMR determinants. Understanding what leads to the emergence of new high-risk lineages is essential to form an early-warning system for the emergence of high-risk clones, and focus efforts of infection control on these, especially when resources are limited.