AUTHOR=Hu Dakang , Chen Wenjie , Wang Weiwen , Tian Dongxing , Fu Pan , Ren Ping , Mu Qing , Li Gang , Jiang Xiaofei 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1147855

DOI=10.3389/fcimb.2023.1147855

ISSN=2235-2988

ABSTRACT=<sec><title>Purpose</title><p>To investigate the mechanisms of <italic>Klebsiella pneumoniae</italic>-induced pyogenic liver abscess (PLA).</p></sec><sec><title>Methods</title><p>Forty-three <italic>K. pneumoniae</italic> 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 <italic>wzi</italic>, <italic>wzy-K1</italic>, and <italic>wzi</italic>+<italic>wzy-K1</italic> were deleted in <italic>K. pneumoniae</italic> NTUH-K2044. Various analyses, such as transmission electron microscopy, neutrophil killing tests, and mouse lethality tests, were used to confirm the consequent changes.</p></sec><sec><title>Results</title><p>Differences were found between <italic>K. pneumoniae</italic> strains from PLA and non-PLA samples for virulence genes and factors, including metabolism genes (<italic>allS</italic> and <italic>peg-344</italic>), capsular polysaccharide (CPS)-synthesis channel gene (<italic>wzy-K1</italic>), CPS-regulating genes (<italic>p-rmpA</italic>, <italic>p-rmpA2</italic>, and <italic>c-rmpA</italic>), and siderophore genes (<italic>iucA</italic> and <italic>iroN</italic>). When <italic>wzy-K1</italic> was positive, the difference between PLA and non-PLA samples was only observed with <italic>c-rmpA</italic>. Δ<italic>wzi</italic>, Δ<italic>wzy-K1</italic>, and Δ<italic>wzi</italic>Δ<italic>wzy-K1</italic> 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<italic>wzi</italic>, Δ<italic>wzy-K1</italic>, and Δ<italic>wzi</italic>Δ<italic>wzy-K1</italic> groups. Lower IL-1β and higher tumor necrosis factor-α secretions were observed for Δ<italic>wzi</italic>, Δ<italic>wzy-K1</italic>, and Δ<italic>wzi</italic>Δ<italic>wzy-K1</italic>.</p></sec><sec><title>Conclusions</title><p>Hypercapsule production is the cornerstone of hypervirulence, regardless of exopolysaccharides. K1 <italic>K. pneumoniae</italic>-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 <italic>K. pneumoniae</italic>.</p></sec>