β-Nicotinamide mononucleotide protects against hypervirulent Klebsiella pneumoniae bloodstream infection and liver injury.

In clinical practice, hypervirulent Klebsiella pneumoniae (hvKP) often causes bloodstream infections (BSI) and liver abscesses; however, the mechanism of hvKP-induced liver abscess formation remains unclear. β-Nicotinamide mononucleotide (NMN) has been reported to have potential therapeutic effects on sepsis, but its impact on hvKP BSI is still unclear. Supplementation with NMN improved the survival rate of hvKP BSI, and the protective effects of NMN disappeared after macrophage depletion. NMN treatment can reduce NF-κB signaling pathway activation in bone marrow-derived macrophages (BMDM) after hvKP infection, as well as the transcription of Il6, Il1b, Tnf, and Cxcl2. NMN, combined with antibiotic therapy, blocked the formation of hvKP liver abscesses. The treatment regimen of NMN combined with antibiotics effectively reduced the levels of inflammatory factors in the liver, inhibited the activation of the NF-κB signaling pathway, and reduced the infiltration of neutrophils into the liver. These results indicate that NMN exerts a protective effect against hvKP BSI by inhibiting excessive inflammatory response, and NMN has therapeutic potential for preventing liver injury caused by hvKP.IMPORTANCEThis study found that β-nicotinamide mononucleotide (NMN) can protect mice against hvKP BSI via inhibiting the NF-κB signaling pathway activation. Supplementing NMN with antibiotic treatment alleviated the inflammatory response of the liver and reduced the formation of liver abscess, providing insight into the mechanism of liver abscess research.