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

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

doi:10.3389/fcimb.2023.1147855

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

Front Cell Infect Microbiol. 2023 Mar 31:13:1147855. doi: 10.3389/fcimb.2023.1147855. eCollection 2023.

Authors

Dakang Hu¹, Wenjie Chen², Weiwen Wang¹, Dongxing Tian¹, Pan Fu^{3

1}, Ping Ren⁴, Qing Mu⁵, Gang Li⁶, Xiaofei Jiang¹

Affiliations

¹ Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
³ Microbiology Department, Children's Hospital of Fudan University, Shanghai, China.
⁴ Zhejiang Provincial Demonstration Centre of Laboratory Medicine Experimental Teaching, Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁵ School of Pharmacy, Fudan University, Shanghai, China.
⁶ Department of Laboratory Medicine, Jinshan Hospital of Fudan University, Shanghai, China.

Abstract

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. Δwzi, Δwzy-K1, and ΔwziΔwzy-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, Δwzi, Δwzy-K1, and ΔwziΔwzy-K1 groups. Lower IL-1β and higher tumor necrosis factor-α secretions were observed for Δwzi, Δwzy-K1, and ΔwziΔwzy-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.

Keywords: Klebsiella pneumoniae; hypervirulence; mechanism; mouse lethality test; pyogenic liver abscess.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines / metabolism
Klebsiella Infections*
Klebsiella pneumoniae
Liver Abscess, Pyogenic*
Mice
Virulence
Virulence Factors / genetics
Virulence Factors / metabolism

Substances

Virulence Factors
Cytokines

Grants and funding

This study was funded by research grants from the National Natural Science Foundation of China (grants 81871692 and 81572031), Shanghai Municipal Key Clinical Specialty (Laboratory Medicine, grant No. shslczdzk03303), and the Shanghai Municipal Science and Technology Commission (grant No. 19JC1413002). The fundings have no role in study design, data collection, the writing of the manuscript and decision to submit it for publication.