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Войти в исследования Infection and drug resistance · 2026
Metformin Enhances Macrophage Phagocytosis and Intracellular Clearance of Hypervirulent Klebsiella pneumoniaevia AMPK Activation.
СтатьяНазвание и аннотация: Перевод в очереди
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Lin YingYing, Li PeiFen, Chen WenBiao, Huang JiaMing, Jiang AoRan, Miao DanDan, Huang DongHong, Xu YuJin
Аннотация
PURPOSE: Hypervirulent Klebsiella pneumoniae (hvKp) evades antibiotics and drives inflammation by surviving within macrophages. This study explored metformin (MET), a common AMP-activated protein kinase (AMPK) activator, as a host-directed therapy against hvKp.
PATIENTS AND METHODS: Using hvKp strain NTUH-K2044-infected THP-1 macrophages, assays measured intracellular bacterial survival, autophagy flux, phagocytosis, and cytokine expression. AMPK-autophagy involvement was tested with agonists/inhibitors and siRNA. A murine liver abscess model assessed MET's efficacy on bacterial burden and immunopathology.
RESULTS: MET reduced intracellular hvKp in macrophages and improved phagocytosis. It activated AMPK, restored autophagy, and increased phagosome-lysosome fusion-effects blocked by AMPK or autophagy inhibition. MET also lowered pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). In mice, MET monotherapy decreased liver bacterial loads and reduced tissue damage and inflammation.
CONCLUSION: MET reprograms macrophages to clear intracellular hvKp through AMPK-driven autophagy and phagocytosis while curbing excessive inflammation, showing promise as a host-directed adjunctive therapy for persistent hvKp infections.
PATIENTS AND METHODS: Using hvKp strain NTUH-K2044-infected THP-1 macrophages, assays measured intracellular bacterial survival, autophagy flux, phagocytosis, and cytokine expression. AMPK-autophagy involvement was tested with agonists/inhibitors and siRNA. A murine liver abscess model assessed MET's efficacy on bacterial burden and immunopathology.
RESULTS: MET reduced intracellular hvKp in macrophages and improved phagocytosis. It activated AMPK, restored autophagy, and increased phagosome-lysosome fusion-effects blocked by AMPK or autophagy inhibition. MET also lowered pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). In mice, MET monotherapy decreased liver bacterial loads and reduced tissue damage and inflammation.
CONCLUSION: MET reprograms macrophages to clear intracellular hvKp through AMPK-driven autophagy and phagocytosis while curbing excessive inflammation, showing promise as a host-directed adjunctive therapy for persistent hvKp infections.