Hypervirulent Klebsiella pneumoniae is the leading cause of mono-microbial induced liver abscess in Asia and beyond. Over 80% of the liver abscess isolates belong to clonal group 23 (CG23) sublineage 1, which is characterized by the presence of a large virulence plasmid as well as two chromosomally integrated mobile genetic elements, genomic island E492 (GIE492) and integrative conjugative element ICEKp10. The CG23-I lineage has rapidly disseminated across the world and can cause disease in healthy individuals. In recent years, we and others have also documented the ease in which hypervirulent K. pneumoniae acquire carbapenem-resistance through broad-host range plasmids, with the potential creation of “superbugs”. Our recent work involves examining the contribution of capsule, the 200kb large virulence plasmid, genomic islands GIE492 and ICEKp10 to bacterial pathogenesis in the mammalian host. We discover how these factors are intertwined in contributing to the survival and fitness of the bacteria in different niches. In particular, we uncover a novel regulator on the virulence plasmid that mediates chromosomal crosstalk to regulate the Type 3 fimbriae in response to iron. This inverse switch with capsule mucoidy promotes bacterial lifestyle switching. In the gut, we found that microcin E492 and the genotoxic colibactin encoded on ICEKp10 cooperatively help in bacterial colonization in the gut. They are able to kill other bacterial species and modify the gut microbiome. The acquisition of all these mobile genetic elements in K. pneumoniae has reengineered the normally nosocomial bacterium to become a pathogen that warrants attention.