CHU HON WENG, WILSONDEAN'S OFFICE (MEDICINE)2023-06-302023-06-302023-01-05CHU HON WENG, WILSON (2023-01-05). THE ROLE OF LARGE VIRULENCE PLASMID IN HYPERVIRULENT KLEBSIELLA PNEUMONIAE. ScholarBank@NUS Repository.https://scholarbank.nus.edu.sg/handle/10635/242645The CG23-I sublineage of hypervirulent Klebsiella pneumoniae is responsible for 80% of Klebsiella-induced liver abscess infections and possess a large virulence plasmid (KpVP). We discover a KpVP-encoded protein IroP that suppresses transcription of Type 3 Fimbriae (T3F) cluster on the bacterial chromosome and is itself suppressed by the Ferric Uptake Regulator (Fur). Iron-rich condition activates Fur which increases T3F expression while decreasing hypermucoid capsule production, causing higher biofilm formation and epithelial cell adhesion. Conversely, iron-limiting condition causes a switch to hypermucoid capsule production and low T3F expression. T3F upregulation also increases in vivo gut colonization. This regulatory switch allows hypervirulent K. pneumoniae to alternate between states favoring dissemination or attachment and colonization in response to iron availability. The acquisition of IroP from other species and integration into the genetic circuitry of the host represents a powerful example of plasmid-chromosomal crosstalk that could contribute to the evolutionary success of the pathogen.enType 3 Fimbriae, Klebsiella pneumoniae, large virulence plasmidThesis0000-0002-2861-945X