Hypercapsule is the cornerstone of Klebsiella pneumoniae in inducing pyogenic liver abscess.

PURPOSE: To investigate the mechanisms of Klebsiella pneumoniae -induced pyogenic liver abscess (PLA).

METHODS: Forty-three K. pneumoniae strains from PLAs and 436 from non-PLAs were collected. Their differences were compared for virulence genes and factors, sequence types, and serotypes. Virulence genes wzi , wzy-K1 , and wzi + wzy-K1 were deleted in K. pneumoniae NTUH-K2044. Various analyses, such as transmission electron microscopy, neutrophil killing tests, and mouse lethality tests, were used to confirm the consequent changes.

RESULTS: Differences were found between K. pneumoniae strains from PLA and non-PLA samples for virulence genes and factors, including metabolism genes ( allS and peg-344 ), capsular polysaccharide (CPS)-synthesis channel gene ( wzy-K1 ), CPS-regulating genes ( p-rmpA , p-rmpA2 , and c-rmpA ), and siderophore genes ( iucA and iroN ). When wzy-K1 was positive, the difference between PLA and non-PLA samples was only observed with c-rmpA . Δ wzi , Δ wzy-K1 , and Δ wzi Δ wzy-K1 strains reverted to hypovirulence. In the Kupffer cell stimulation assay, interleukin (IL)-6, IL-12, IL-10, and transforming growth factor-β secretions were found to be equivalent in NTUH-K2044, Δ wzi , Δ wzy-K1 , and Δ wzi Δ wzy-K1 groups. Lower IL-1β and higher tumor necrosis factor-α secretions were observed for Δ wzi , Δ wzy-K1 , and Δ wzi Δ wzy-K1 .

CONCLUSIONS: Hypercapsule production is the cornerstone of hypervirulence, regardless of exopolysaccharides. K1 K. pneumoniae -induced PLA may decrease core inflammatory cytokines rather than increase anti-inflammatory cytokines. Exopolysaccharides could also attenuate the inflammatory response to aid in the immune escape of K. pneumoniae .