Host interactions with hypervirulent Klebsiella pneumoniae along the gut-liver axis

Hypervirulent Klebsiella pneumoniae (hvKp) represents an emerging global health threat, distinguished by enhanced virulence traits that enable it to breach the protective barriers of the gut-liver axis to cause liver abscesses that can subsequently metastasize to distal organs. Yet hvKp must contend with formidable barriers in the gastrointestinal tract that normally prevent bacterial translocation into extraintestinal sites. In this review, we examine current knowledge on the mechanisms of hvKp gut translocation and subsequent liver abscess formation, focusing on the interplay between hvKp and host immune responses along the gut-liver axis. We discuss findings across studies concerning hvKp-Kupffer cells interaction during extraintestinal dissemination, with particular emphasis on the role of phagocytosis and intracellular survival within macrophages in mediating liver abscess formation. We highlight the strengths and limitations of current murine models in faithfully recapitulating the continuum of hvKp pathogenesis and disease, especially since strain-specific and model-dependent outcomes may not be generalizable. Addressing knowledge gaps and resolving conflicting findings through well-characterized hvKp strains, diverse experimental approaches coupled with robust KLA models, are essential for advancing research in hvKp pathogenesis so as to inform the development of effective therapeutic and preventive strategies.