A low-molecular-weight α-glucan from edible fungus Agaricus blazei Murrill activates macrophage TFEB-mediated antibacterial defense to combat implant-associated infection

• Published in: Carbohydrate polymers 2024-12, Vol.346, p.122659, Article 122659
• Main Authors: Wang, Qishan, Wang, Yuehong, Liu, Yihao, Yuan, Kai, Lin, Yixuan, Qian, Xian, Pei, Hongyan, Weng, Liangliang, Fan, Kaijian, Hu, Yihe, Yang, Yiqi
• Format: Article
• Language: English
• Subjects: Agaricus - chemistry; Agaricus blazei Murrill polysaccharide; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial immunity; Autophagy - drug effects; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Glucans - chemistry; Glucans - pharmacology; Implant-associated infection; Macrophage; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Molecular Weight; Prosthesis-Related Infections - drug therapy; RAW 264.7 Cells; TFEB
• ISSN: 0144-8617; 1879-1344; 1879-1344
• DOI: 10.1016/j.carbpol.2024.122659

Implant-associated infection (IAI) is a prevalent and potentially fatal complication of orthopaedic surgery. Boosting antibacterial immunity, particularly the macrophage-mediated response, presents a promising therapeutic approach for managing persistent infections. In this study, we successfully isolated and purified a homogeneous and neutral water-soluble polysaccharide, designated as AM-1, from the edible fungus Agaricus blazei Murrill. Structure analysis revealed that AM-1 (Mw = 3.87 kDa) was a low-molecular-weight glucan characterized by a primary chain of →4)-α-D-Glcp-(1 → and side chains that were linked at the O-6 and O-3 positions. In vivo assays showed that AM-1 effectively attenuated the progression of infection and mitigated infectious bone destruction in IAI mouse models. Mechanistically, AM-1 promotes intracellular autophagy-lysosomal biogenesis by inducing the nuclear translocation of transcription factor EB, finally enhancing the bactericidal capabilities and immune-modulatory functions of macrophages. These findings demonstrate that AM-1 significantly alleviates the progression of challenging IAIs as a presurgical immunoenhancer. Our research introduces a novel therapeutic strategy that employs natural polysaccharides to combat refractory infections. [Display omitted] •A homogeneous α-glucan (AM-1) is purified from the edible fungus Agaricus blazei Murrill.•AM-1 enhances macrophages' autophagy flux and bactericidal behavior, depending on TFEB.•AM-1 boosts the antibacterial response of macrophages to alleviate IAI progression.•AM-1 is an efficient immunotherapeutic agent for managing stubborn IAI.