Synergy of bacteriophage depolymerase with host immunity rescues sepsis mice infected with hypervirulent Klebsiella pneumoniae of capsule type K2.

Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE

Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Austin, Tex. : Landes Bioscience

Klebsiella pneumoniae*/pathogenicity ; Klebsiella pneumoniae*/immunology ; Klebsiella Infections*/immunology ; Klebsiella Infections*/therapy ; Klebsiella Infections*/microbiology ; Sepsis*/immunology ; Sepsis*/microbiology ; Bacterial Capsules*/immunology ; Bacteriophages*/genetics; Animals ; Mice ; Glycoside Hydrolases/genetics ; Female ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Virulence

The hypervirulent Klebsiella pneumoniae (hvKp) with K1 and K2 capsular types causes liver abscess, pneumonia, sepsis, and invasive infections with high lethality. The presence of capsular polysaccharide (CPS) resists phagocytic engulfment and contributes to excessive inflammatory responses. Bacteriophage depolymerases can specifically target bacterial CPS, neutralizing its defense. Based on our previous research, we expressed and purified a bacteriophage depolymerase (Dep1979) targeting hvKp with capsule type K2. Interestingly, although Dep1979 lacked direct bactericidal activity in vitro , it exhibited potent antibacterial activity in vivo . Low-dose Dep1979 (0.1 mg/kg) improved the 7-day survival of immunocompetent mice to 100%. Even at 0.01 mg/kg, mice achieved 100% survival at 5 days, although efficacy sharply declined at doses as low as 0.001 mg/kg. Following Dep1979 treatment, reduced expression of inflammatory factors and no apparent tissue damage were observed. However, therapeutic efficacy significantly diminished in immunosuppressed mice. These findings underscore the critical role of Dep1979 in disarming CPS, which synergizes with host immunity to enhance antibacterial activity against hvKp.

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Keywords: Hypervirulent K. pneumoniae; anti-virulence agent; capsular polysaccharide; host immunity; phage depolymerase; sepsis

EC 3.2.1.- (Glycoside Hydrolases)
EC 3.2.1.87 (capsular-polysaccharide galactohydrolase)
0 (Anti-Bacterial Agents)

Date Created: 20241021 Date Completed: 20241021 Latest Revision: 20241025

20241025

PMC11497950

10.1080/21505594.2024.2415945

39429194