Cao Zubai, Meng Bao, Chen Jie, Ge Ruomu, Liu Yanyan, Li Jiabin
Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Anhui Province Key Laboratory of Infectious Diseases & Institute of Bacterial Resistance, Anhui Medical University, Hefei, China.
mSphere. 2025 Aug 26;10(8):e0036125. doi: 10.1128/msphere.00361-25. Epub 2025 Jul 31.
In clinical practice, hypervirulent (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 , , , and . 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.
在临床实践中，高毒力肺炎克雷伯菌（hvKP）常引起血流感染（BSI）和肝脓肿；然而，hvKP诱导肝脓肿形成的机制仍不清楚。据报道，β-烟酰胺单核苷酸（NMN）对脓毒症具有潜在治疗作用，但其对hvKP BSI的影响仍不明确。补充NMN可提高hvKP BSI的存活率，巨噬细胞耗竭后NMN的保护作用消失。NMN治疗可降低hvKP感染后骨髓来源巨噬细胞（BMDM）中NF-κB信号通路的激活，以及 、 、 和 的转录。NMN与抗生素联合治疗可阻止hvKP肝脓肿的形成。NMN联合抗生素的治疗方案有效降低了肝脏中炎症因子的水平，抑制了NF-κB信号通路的激活，并减少了中性粒细胞向肝脏的浸润。这些结果表明，NMN通过抑制过度的炎症反应对hvKP BSI发挥保护作用，且NMN对预防hvKP引起的肝损伤具有治疗潜力。
重要性
本研究发现，β-烟酰胺单核苷酸（NMN）可通过抑制NF-κB信号通路激活来保护小鼠免受hvKP BSI侵害。NMN与抗生素治疗联合使用可减轻肝脏的炎症反应并减少肝脓肿的形成，为肝脓肿研究机制提供了见解。
