Antibacterial and Immunomodulatory Activities of a Natural Polysaccharide Against Staphylococcus aureus Infection

ABSTRACT Over decades, the growing prevalence of antibiotic‐resistant bacterial infections, including rhinosinusitis caused by Staphylococcus aureus , has represented a significant public health challenge. The emergence of multidrug‐resistant strains and biofilm formation has limited the efficacy of conventional antibiotics, leading to increased patient morbidity and an urgent need to explore alternative therapeutic agents. Polygonatum kingianum polysaccharides (PKP), key bioactive components derived from traditional herbs, have attracted attention for their broad pharmacological effects. However, a thorough evaluation of their antibacterial potential in complex in vivo infection models remains lacking. Herein, we report the extraction of PKP and a comprehensive assessment of its antibacterial activity both in vitro and in vivo. In vitro, PKP exhibited potent, concentration‐dependent antibacterial activity against S. aureus and Escherichia coli , with significantly stronger bactericidal activity against the Gram‐positive bacterium (89.8% at 400 mg/mL; MIC = 400 mg/mL; MBC = 700 mg/mL). The antibacterial mechanism appeared to involve disruption of the cell membrane, with structural differences among bacterial envelopes likely explaining the variation in efficacy. Furthermore, in a rat model of S. aureus ‐induced rhinosinusitis, intranasal administration of PKP effectively attenuated bacterial infection, as evidenced by significantly reduced neutrophilic infiltration and abscess formation, as well as decreased levels of the pro‐inflammatory cytokine interleukin‐6 (IL‐6). Meanwhile, PKP helped restore the barrier‐protective cytokine IL‐22. Hematological profiles further confirmed the systemic anti‐inflammatory and immunomodulatory effects of PKP, including regulation of leukocyte counts and improvement of immune organ indices. This study demonstrated that PKP exhibited significant in vitro and in vivo antibacterial activity against S. aureus through a dual mechanism of direct bactericidal action and modulation of the immune response. Overall, these findings suggest that PKP has great potential as a natural therapeutic agent for bacterial rhinosinusitis.