How Klebsiella pneumoniae controls its virulence

The bacterial pathogen Klebsiella pneumoniae is a serious public health threat due to its propensity to develop antimicrobial resistance (AMR), the emergence of hypervirulent strains able to cause community-acquired infections, and the more recent development of convergent strains that exhibit both traits. Pathogenesis in K. pneumoniae is attributed to a range of largely horizontally-acquired virulence or fitness factors that collectively mediate immune evasion, attachment, intermicrobial competition and nutrition in different niches within the host. An outstanding research question is how expression of these factors is coordinated during infection, and how this regulatory control varies in genomically distinct lineages. Here we review recent progress in understanding the regulators and networks that control K. pneumoniae virulence or host fitness factor expression, discuss the role of plasmid-chromosome regulatory crosstalk in pathogenesis, and explore the potential of new global approaches to enhance our understanding. This knowledge will be instrumental in accurately predicting virulence from genome sequence in new emergent K. pneumoniae lineages, in order to track and manage this priority pathogen.