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螺旋轮环藤(L.)曼斯菲尔德提取物增强了一些β-内酰胺类抗生素对耐β-内酰胺类葡萄球菌的抗菌活性。

Boesenbergia rotunda (L.) Mansf. extract potentiates the antibacterial activity of some β-lactams against β-lactam-resistant staphylococci.

机构信息

School of Preclinic, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.

School of Biology, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.

出版信息

J Glob Antimicrob Resist. 2018 Mar;12:207-213. doi: 10.1016/j.jgar.2017.10.019. Epub 2017 Nov 2.

Abstract

OBJECTIVES

The purpose of this study was to investigate the effect of Boesenbergia rotunda (L.) Mansf. extract (BRE) and peptidoglycan inhibitor antibiotics, alone and in combination, against β-lactam-resistant staphylococci.

METHODS

Antibacterial and synergistic activities of BRE alone and in combination with ampicillin (AMP), cloxacillin (CLX), cefazolin (CZO) or vancomycin (VAN) were evaluated against two β-lactam-resistant Staphylococcus aureus (BRSA) isolates and one β-lactam-resistant Staphylococcus epidermidis (BRSE) isolate. The activities were confirmed by killing curve assays. The preliminary antimicrobial action was elucidated by transmission electron microscopy (TEM) and cytoplasmic membrane (CM) permeability assay.

RESULTS

All tested staphylococci were inhibited by BRE at a minimum inhibitory concentration (MIC) of 16μg/mL. Two BRSA strains showed high resistance to CLX, AMP and CZO, whilst BRSE was resistant to CLX and AMP. All tested isolates remained susceptible to VAN. Chequerboard assay demonstrated a fractional inhibitory concentration index (FICI) of 0.50 for the BRE+CLX combination against the BRSA strains. Killing curve determinations confirmed the antibacterial and synergistic activities. TEM revealed collapse of the CM in BRE-treated cells and damage both of the CM and peptidoglycan (PG) in BRE+CLX-treated cells. The CM permeability assay showed that either BRE or nisin alone as well as BRE+CLX significantly induced leakage of OD-absorbing materials.

CONCLUSIONS

BRE potentiated the activity of β-lactams, particularly CLX, against β-lactam-resistant staphylococci by damaging the CM and PG layer, leading to leakage of intracellular material. Combination of BRE and β-lactams provides a potential way forward in developing novel antistaphylococcal agents.

摘要

目的

本研究旨在探讨蓬莪术(L.)Mansf.提取物(BRE)与肽聚糖抑制剂抗生素单独及联合应用对β-内酰胺类耐药葡萄球菌的作用。

方法

采用杀菌曲线法评价 BRE 单独及与氨苄西林(AMP)、氯唑西林(CLX)、头孢唑林(CZO)或万古霉素(VAN)联合应用对 2 株β-内酰胺类耐药金黄色葡萄球菌(BRSA)和 1 株β-内酰胺类耐药表皮葡萄球菌(BRSE)的抗菌和协同活性。透射电镜(TEM)和细胞质膜(CM)通透性试验初步阐明了其抗菌作用机制。

结果

所有测试的葡萄球菌均被 MIC 为 16μg/ml 的 BRE 抑制。两株 BRSA 株对 CLX、AMP 和 CZO 表现出高度耐药,而 BRSE 则对 CLX 和 AMP 耐药。所有测试的分离株均对 VAN 敏感。棋盘微量稀释法显示 BRE+CLX 组合对 BRSA 株的部分抑菌浓度指数(FICI)为 0.50。杀菌曲线测定证实了其抗菌和协同作用。TEM 显示 BRE 处理的细胞 CM 崩溃,BRE+CLX 处理的细胞 CM 和肽聚糖(PG)均受损。CM 通透性试验表明,BRE 或乳链菌肽(nisin)单独以及 BRE+CLX 均显著诱导 OD 吸收物质的渗漏。

结论

BRE 通过破坏 CM 和 PG 层,导致细胞内物质渗漏,增强了β-内酰胺类药物,特别是 CLX,对β-内酰胺类耐药葡萄球菌的活性。BRE 与β-内酰胺类药物的联合应用为开发新型抗葡萄球菌药物提供了一种潜在的方法。

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