Screening of natural products targeting PBP3 and their synergistic effects with antibiotics in inhibiting Streptococcus pneumoniae

IF 4.8 1区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Food Bioscience Pub Date : 2025-06-12 DOI:10.1016/j.fbio.2025.107054

Zhuodi Wu , Yimeng Chen , Yu Cui , Doudou Yang , Guanjie Zhao , Qian Li , Dandan Zhang , Yinku Liang

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引用次数: 0

Abstract

With the increasing resistance of Streptococcus pneumoniae (S. pneumoniae) to β-lactam antibiotics (BLAs), combination therapy has become an effective strategy to address this challenge. This study evaluated the inhibitory activity of ten natural medicines against S. pneumoniae using in vitro antibacterial assays. Seven herbs, including Galla chinensis, Coptidis rhizoma, Scutellaria baicalensis, Phellodendri chinensis cortex, Sophora flavescens, Salviae miltiorrhizae radix et rhizoma, and Houttuynia cordata Thunb, were found to be effective, with Coptidis rhizoma, Scutellaria baicalensis, and Phellodendri chinensis cortex showing the most significant activity. Additionally, surface plasmon resonance (SPR) technology was employed to couple the PBP3 target to a CM5 chip for target-guided fishing of potential active compounds and evaluation of their PBP3-binding capabilities. The ethanol extract of Scutellaria baicalensis exhibited the highest binding response, reaching 20,000 RU. The target-bound components were eluted and identified by UPLC-MS, confirming Oroxindin as the most potent target compound. Its dissociation constant (KD) with PBP3 was determined to be 5.049 × 10⁻⁷ mol/L, indicating stable binding and high affinity. Finally, it is noteworthy that in vitro antibacterial assays demonstrated a significant enhancement of antibiotic efficacy by Oroxindin: co-administration with cefquinome (CEF) reduced the minimum inhibitory concentration (MIC) for S. pneumoniae from 32 μg/mL to 1 μg/mL (a 32-fold increase in sensitivity), while co-administration with ampicillin (AMP) reduced the MIC from 32 μg/mL to 0.5 μg/mL (a 64-fold increase in sensitivity). This study identified and validated the sensitizing efficacy of Oroxindin in inhibiting S. pneumoniae, providing a new approach to addressing BLAs resistance and laying a foundation for mechanistic research and clinical translation of combination therapy strategies.

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靶向PBP3的天然产物筛选及其与抗生素协同抑制肺炎链球菌的作用

随着肺炎链球菌（S. pneumoniae）对β-内酰胺类抗生素（BLAs）耐药性的增加，联合治疗已成为应对这一挑战的有效策略。本研究采用体外抑菌法评价了10种天然药物对肺炎链球菌的抑菌活性。结果表明，五倍子、黄连、黄芩、黄柏皮、苦参、丹参、鱼腥草等7种中药均有较好的效果，其中黄连、黄芩和黄柏皮的效果最显著。此外，利用表面等离子体共振（SPR）技术将PBP3靶点与CM5芯片耦合，用于靶向引导的潜在活性化合物的捕获和PBP3结合能力的评估。黄芩乙醇提取物的结合响应最高，达到20,000 RU。通过UPLC-MS对目标结合成分进行洗脱和鉴定，确定Oroxindin为最有效的目标化合物。测定其与PBP3的解离常数（KD）为5.049 × 10−7 mol/L，结合稳定，亲和力高。最后，值得注意的是，体外抗菌试验显示，奥罗辛定显著增强了抗菌效果：与头孢醌（CEF）合用可将肺炎链球菌的最低抑制浓度（MIC）从32 μg/mL降至1 μg/mL（敏感性提高32倍），而与氨苄西林（AMP）合用可将MIC从32 μg/mL降至0.5 μg/mL（敏感性提高64倍）。本研究鉴定并验证了Oroxindin抑制肺炎链球菌的增敏效果，为解决BLAs耐药提供了新的途径，为联合治疗策略的机理研究和临床转化奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food Bioscience Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

6.40

自引率

5.80%

发文量

671

审稿时长

27 days

期刊介绍： Food Bioscience is a peer-reviewed journal that aims to provide a forum for recent developments in the field of bio-related food research. The journal focuses on both fundamental and applied research worldwide, with special attention to ethnic and cultural aspects of food bioresearch.