KpFhaB/FhaC is a virulence-associated TPS system of the globally-disseminated Klebsiella pneumoniae ST15 high-risk clone

Abstract

[Abstract] Introduction: The global dissemination of Klebsiella pneumoniae sequence type 15 (ST15), a Q9 high-risk clone frequently resistant to carbapenems and third-generation cephalosporins, represents a major public health concern. While chaperone-usher pili (CUP) systems (i.e. Kpi system) are known mediators of K. pneumoniae adhesion and biofilm formation, additional adhesin mechanisms remain poorly characterized in this pathogen. In this study, we identified and functionally characterized a two-partner secretion (TPS) system, KpFhaB/FhaC, in the outbreak strain K. pneumoniae Kp3380 (ST15).

Methods: Genomic and bioinformatic analyses were performed to identify and characterize the KpFhaB/FhaC TPS system. Knockout strains lacking fhaC, Kpi system, or both were constructed for functional studies. Biofilm formation, epithelial cell adhesion, bacterial fitness, and in vivo intestinal colonization were evaluated using in vitro and murine models.

Results: KpFhaB/FhaC was identified as a conserved TPS system associated with the K. pneumoniae ST15 high-risk clone. It promotes biofilm formation and adhesion to human colorectal epithelial cells. Combined inactivation with the Kpi pili system produced an additive reduction in these phenotypes, indicating complementary roles in adhesion. Inactivation of KpFhaB/FhaC resulted in a significant fitness cost, whereas it did not significantly affect intestinal colonization in vivo.

Discussion: These results suggest a functional specialization between both systems in K. pneumoniae ST15, suggesting that retaining them could give a selective advantage for this high-risk clone. Overall, our findings indicate that KpFhaB/FhaC is a conserved, chromosomally encoded TPS system that positively contributes to adhesion, biofilm formation and bacterial fitness in K. pneumoniae ST15.