Phage depolymerase modulates virulence and biofilm in hypervirulent Klebsiella pneumoniae by CPS-mediated suppression of type 3 fimbriae

Phage-derived depolymerases represent a promising antibiotic alternative for treating Klebsiella pneumoniae infections. They function by specifically degrading capsular polysaccharide (CPS), thereby sensitizing bacteria to the host immune system and complement-mediated killing. However, the impact of depolymerases on bacterial biofilm formation remains unclear. Our study revealed that hypervirulent K. pneumoniae (hvKp) strains with thick CPS layers exhibit relatively weak biofilm formation. Intriguingly, depolymerase treatment enhanced their biofilm-forming capacity. Mechanistically, depolymerase-mediated degradation of CPS relieved its repression on the type 3 fimbriae gene cluster mrkABCDF, thereby promoting biofilm formation. In vivo experiments in a mouse model further demonstrated that CPS also inhibits the virulence functions associated with type 3 fimbriae. More importantly, this CPS-mediated suppression of biofilm appears to be a common phenomenon among hvKp strains. In summary, by elucidating the dual role of depolymerase in modulating both virulence and biofilm in hvKp, our work uncovers a potential interaction between CPS and type 3 fimbriae, providing deeper insights into the pathogenicity of this clinically important bacterium.