Comparing the evolution and virulence of the carbapenem resistant Klebsiella pneumoniae (CRKP) clones and their plasmids in Europe and China

The emergence and spread of antibiotic-resistant bacteria poses a significant threat to public health worldwide. Klebsiella pneumoniae is recognized as a particularly problematic species due to the spread of strains that are resistant to carbapenems (an important class of antibiotics) within hospital settings. Genes that confer resistance or virulence properties are often carried by genetic elements called plasmids. Plasmids can replicate and transfer independently between bacteria, which can account for how quickly these genes can spread across different bacteria. Moreover, different strains (and presumably different plasmids), are spreading in different parts of the world. ST11 is widespread in China, ST307 is one of the fastest spreading strains in Europe. Both of these strains attracted attention due to their high prevalence and ability to cause severe infections. Understanding the evolutionary mechanisms underpinning the emergence and spread (of both the bacteria and the plasmids), and the pathogenicity, of these strains is crucial for developing effective strategies to combat their spread and improve patient outcomes. For example - ST11 strains have been reported that contain plasmids harbouring both resistance genes and genes that make the bacteria more virulent. These plasmids have probably evolved through two different plasmids combining to form a hybrid, although little is known about the underlying mechanisms nor how common this phenomenon might be. In this project, we aim to investigate and compare the evolution of ST11 and ST307, and their plasmids, at a detailed molecular level. We will use advanced whole genome sequencing technology that provides the means to investigate both the genome of the strains themselves, and of the plasmids that carry resistance and virulence genes. By comparing the evolutionary trajectories, epidemiological patterns, and pathogenic potential of ST11 and ST307, we aim to identify key genetic determinants, processes and conditions that contribute to their success and persistence. This knowledge will enhance our understanding of the factors driving the spread of these clones and inform the development of targeted interventions to control their transmission, as well mitigating the risk from new emerging strains in the future. We will also use experimental evolution techniques to study what makes certain combinations of strain and plasmid successful, to what extent these resistance plasmids can be 'costly' to the bacteria under different conditions, and how free they are to transfer between different strains. Additionally, we will conduct virulence assays to assess the ability of these clones to cause disease. By analyzing their interactions with host cells and studying the factors that contribute to their pathogenicity, we can gain a better understanding of the mechanisms underlying their ability to cause severe infections, and thus contribute to the global efforts in combating antibiotic resistance and improving patient care.