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

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.