Mushroom-derived polysaccharides as broad-spectrum antimicrobial agents: mechanisms, structural modifications, and therapeutic potential

Antibiotic resistance poses one of the most pressing threats to global public health, underscoring the urgent need for novel antimicrobial agents. Mushroom-derived polysaccharides have attracted considerable attention due to their structural diversity, low toxicity and various pharmacological activities. This review provides a comprehensive overview of the antiviral, antibacterial, and antifungal activities of polysaccharides isolated from edible and medicinal mushrooms against a range of pathogens, including multidrug-resistant species, with particular emphasis on the structural features that govern their efficacy. The mechanisms underlying these activities are examined, encompassing host immunomodulation, inhibition of pathogen attachment and entry, enzymatic inhibition of microbial replication and direct disruption of microbial cell integrity. Strategies to enhance antimicrobial potency are also discussed, covering chemical derivatization (e.g., sulfation, deacetylation), nanocomposite formulation and combination with conventional antimicrobials. Finally, the challenges of clinical translation including limited oral bioavailability, structural heterogeneity across preparations, and the lack of randomized clinical trial data in infectious disease indications, are critically evaluated. Addressing these gaps through standardization of production protocols, integrative structure-activity characterization and well-designed clinical trials will help advance the application of mushroom polysaccharides in medicine, food preservation, and agriculture.