一种天然多糖抗金黄色葡萄球菌感染的抗菌与免疫调节活性

文献信息

中文摘要

背景： 数十年来，抗生素耐药性细菌感染（包括由金黄色葡萄球菌引起的鼻窦炎）的患病率不断上升，已成为重大的公共卫生挑战。多重耐药菌株的出现和生物膜形成限制了传统抗生素的疗效，导致患者发病率增加，并迫切需要探索替代治疗药物。滇黄精多糖（PKP）是源自传统草药的关键生物活性成分，因其广泛的药理作用而受到关注。然而，对其在复杂体内感染模型中的抗菌潜力仍缺乏全面评估。方法：在此，我们报道了PKP的提取及其体外和体内抗菌活性的综合评估。结果：在体外，PKP对金黄色葡萄球菌和大肠杆菌表现出强效、浓度依赖性的抗菌活性，对革兰阳性菌的杀菌活性显著更强（400 mg/mL时为89.8%；MIC = 400 mg/mL；MBC = 700 mg/mL）。抗菌机制似乎涉及破坏细胞膜，细菌包膜之间的结构差异可能解释了疗效差异。此外，在金黄色葡萄球菌诱导的大鼠鼻窦炎模型中，鼻内给予PKP有效减轻了细菌感染，表现为中性粒细胞浸润和脓肿形成显著减少，以及促炎细胞因子白细胞介素-6（IL-6）水平降低。同时，PKP有助于恢复屏障保护性细胞因子IL-22。血液学特征进一步证实了PKP的全身抗炎和免疫调节作用，包括调节白细胞计数和改善免疫器官指数。结论：本研究表明，PKP通过直接杀菌作用和调节免疫反应的双重机制，对金黄色葡萄球菌表现出显著的体外和体内抗菌活性。总体而言，这些发现表明PKP作为细菌性鼻窦炎的天然治疗剂具有巨大潜力。

英文摘要

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.