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体内抗药性鲍曼不动杆菌肺炎 BALB/c 小鼠模型中土木香提取物及其成分香芹酚和百里酚的抗菌活性。

In vivo antibacterial activity of Zataria multiflora Boiss extract and its components, carvacrol, and thymol, against colistin-resistant Acinetobacter baumannii in a pneumonic BALB/c mouse model.

机构信息

Department of Cellular and Molecular Biology, Faculty of Sciences, Science and Research Brand of Islamic Azad University, Tehran, Iran.

Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Cell Biochem. 2019 Nov;120(11):18640-18649. doi: 10.1002/jcb.28908. Epub 2019 Jul 24.

Abstract

BACKGROUND

Acinetobacter baumannii has emerged as a major cause of nosocomial infections. Various resistance mechanisms of A. baumannii against antibiotics have transformed it into a successful nosocomial pathogen. Because of the limited number of available antibiotics, we used a medicinal plant with an antibacterial effect. Zataria multiflora Boiss (ZMB) extract and its components were used for the treatment of pneumonic mice infected with A. baumannii. The biological effects of this extract and the regulation of the outer membrane protein A (ompA) gene were used in a mouse model.

METHODS

A pneumonic mouse model was prepared using clinical and standard strains (1.5 × 10  colony-forming units/mL) of A. baumannii. BALB/c mice groups were treated with a ZMB extract, carvacrol, thymol, and sensitive antibiotics. The lung tissues of the treated mice were cultured for 5 days and each day, bacterial clearance and the ompA gene expression were assessed by quantitative real-time polymerase chain reaction.

RESULTS

In the lung tissue culture of pneumonic mice infected with standard or clinical isolate, no colony was detected when treated with the ZMB extract after 2 and 3 days (P < 0.01), respectively. In the carvacrol-treated group, bacterial clearance was seen at day 4 and day 5 (P < 0.05). Bacterial clearance was seen 5 days after treatment with thymol and imipenem and 6 days after ampicillin/sulbactam treatment. The regulation of ompA gene was significantly decreased in this order: ZMB extract, carvacrol, thymol, imipenem, and ampicillin/sulbactam.

DISCUSSION

The ZMB extract had a potent bactericidal effect against A. baumannii that could downregulate the ompA gene. ZBM extract and carvacrol could be novel therapeutic agents for antibiotic-resistant A. baumannii.

摘要

背景

鲍曼不动杆菌已成为医院感染的主要原因。鲍曼不动杆菌对各种抗生素的耐药机制使其成为一种成功的医院病原体。由于可用抗生素的数量有限,我们使用了一种具有抗菌作用的药用植物。研究人员采用藏茴香(ZMB)提取物及其成分治疗感染鲍曼不动杆菌的肺炎小鼠。在小鼠模型中研究了该提取物的生物学效应及其对外膜蛋白 A(ompA)基因的调控。

方法

采用临床和标准菌株(1.5×10 菌落形成单位/毫升)制备肺炎小鼠模型。用 ZMB 提取物、香芹酚、百里酚和敏感抗生素处理 BALB/c 小鼠。用 ZMB 提取物处理的小鼠肺组织在第 2 天和第 3 天培养 5 天,每天通过定量实时聚合酶链反应评估细菌清除率和 ompA 基因表达。

结果

在感染标准或临床分离株的肺炎小鼠肺组织培养中,用 ZMB 提取物处理后第 2 天和第 3 天分别未检测到菌落(P<0.01)。在香芹酚处理组中,第 4 天和第 5 天观察到细菌清除(P<0.05)。用百里酚和亚胺培南治疗后第 5 天,用氨苄西林/舒巴坦治疗后第 6 天观察到细菌清除。ompA 基因的调节按以下顺序显著降低:ZMB 提取物、香芹酚、百里酚、亚胺培南和氨苄西林/舒巴坦。

讨论

ZMB 提取物对鲍曼不动杆菌具有很强的杀菌作用,可下调 ompA 基因。ZMB 提取物和香芹酚可能是治疗抗生素耐药鲍曼不动杆菌的新型治疗药物。

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