Hypervirulent Klebsiella pneumoniae (hvKp) is the leading cause of mono-microbial induced liver abscess in Asia and beyond. More than 80% of liver abscess hvKp isolates belong to the K1 serotype from the ST23 lineage. This lineage possesses a single, 200kb non-mobilizable large virulence plasmid (KpVP) that carries virulence factors including the hypermucoviscous capsule phenotype operon (rmp) as well as iron sequestering siderophores aerobactin (iuc) and salmochelin (iro). Bioinformatics analyses of KpVP’s origin suggest that this large virulent plasmid is well conserved and maintained over many generations. Besides contributing to hypermucoviscosity of the capsule and iron acquisition, it is unknown what other roles KpVP play in the bacterial life cycle.
We discovered that a KpVP-cured K1 hvKp strain SGH10 showed transcriptional upregulation of Type 3 Fimbriae (T3F) which are involved in biofilm formation and epithelial cell attachment. A novel gene downstream of the Salmochelin Outer Membrane Receptor iroN was found to translate into an 8.6 kDa protein responsible for suppressing transcription of T3F genes. We designate the novel factor as IroP, which is found in different lineages of hvKp as well. Through pull-down studies and protein mass-spectrometry, we identified potential protein partners that could act in complex with IroP to transcriptionally repress T3F. IroP is in turn repressed by the iron-responsive Ferric Uptake Regulator (Fur). Fur upregulates T3F indirectly through IroP as well as downregulates hypermucoid capsule production. Under iron limited condition, the bacterium produces a hypermucoid capsule with low T3F levels while under iron repletion, the bacterium downregulates capsule and upregulates T3F, resulting in phenotypic changes to hvKp which affects adhesion to epithelial cells and biofilm formation. The cross-talk between plasmid and chromosomal genes might be an adaptation by hvKp to more efficiently coordinate the timely expression of its virulence factors under various environmental niches. I will discuss what are the potential advantages of this cross-regulation and how it might contribute to hvKp’s success as a pathogen.