Differential gut transmission of IncP plasmid clades involving hypervirulent Klebsiella pneumoniae reveals plasmid-specific ecological adaptation.

Conjugative plasmids can drive the global spread of antimicrobial resistance (AMR) in Enterobacterales. Hypervirulent Klebsiella pneumoniae (hvKp) increasingly acquire AMR plasmids, raising concern about convergent hypervirulent drug-resistant clones. Yet little is known about plasmid transmission dynamics in hvKp. Using an antibiotic-perturbed murine gut model with hvKp and human commensal E. coli, we discover that broad-host range IncP plasmids belonging to different phylogenetic branches (clade I (PTU-P1) and clade II (PTU-P2)) transfer differentially in the gut, mirroring the higher prevalence of PTU-P2 plasmids in human-associated samples. Statistical modelling and experimental results show that secondary transfer by transconjugants sustains gut transmission without continuous donor input. Furthermore, the hvKp capsule exerts a modest effect on transfer in vivo compared to in vitro aerobic conditions. Under anaerobic conditions, hvKp capsule mucoviscosity is markedly reduced, and PTU-P2 plasmids conjugate more efficiently than PTU-P1 counterparts. Our findings reveal that the hypermucoviscous capsule may not substantially impede gene exchange in the gut where microenvironments shape plasmid transfer dynamics, highlighting the pitfalls of extrapolating in vitro data to relevant ecological niches. Our work also emphasizes the high-risk nature of gut-adapted PTU-P2 plasmids and the ease with which hvKp can acquire them, underscoring the need for continued surveillance.