Antibacterial Properties of Medicinal Plants From Pakistan Against Multidrug-Resistant ESKAPE Pathogens.

Antibacterial Properties of Medicinal Plants From Pakistan Against Multidrug-Resistant ESKAPE Pathogens.
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DOI:
10.3389/fphar.2018.00815
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发表时间:
2018
影响因子:
5.6
通讯作者:
Quave CL
Quave CL
中科院分区:
医学2区
文献类型:
--
作者:
Khan MF;Tang H;Lyles JT;Pineau R;Mashwani ZU;Quave CL

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巴基斯坦苏德诺蒂地区的当地人拥有丰富的传统医学治疗各种疾病的方法。我们从 Sudhnoti 民族药理学传统中选择了九种用于治疗传染性和炎症性疾病的植物。我们的目的是评估这些物种的提取物对多重耐药 (MDR) ESKAPE(屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属)病原体的体外抗感染潜力。植物标本在巴基斯坦苏德诺蒂地区采集,凭证存放在巴基斯坦和美国。将干燥的散装样品研磨成细粉,并通过水煎剂和乙醇浸渍进行提取。评估提取物对 ESKAPE 病原体的生长抑制活性,并评估金黄色葡萄球菌的生物膜和群体感应活性。通过处理的人角质形成细胞 (HaCaT) 的乳酸脱氢酶测定来评估对人细胞的细胞毒性。四种乙醇提取物(花椒、铁线蕨、苦艾和黄花蒿)抑制 ESKAPE 病原体 MDR 菌株的生长(IC50:256 μg mL−1)。除 Pyrus pashia 和 M. annua 之外,所有提取物在金黄色葡萄球菌 agr I 的报告菌株中均表现出显着的群体淬灭。Z. armatum 果实的乙醇提取物(提取物 1290)抑制 agr I-III 的金黄色葡萄球菌报告菌株中的群体感应(IC50 32–256 μg mL−1)。通过检测细菌上清液中的 δ-毒素来验证提取物 1290 的群体猝灭活性,浓度为 64–256 μg mL−1 足以使 δ-毒素产量显着下降。在亚抑制生长浓度下,没有一种提取物能够抑制金黄色葡萄球菌生物膜的形成。所有提取物均被人类角质形成细胞良好耐受(LD50 ≥ 256 μg mL−1)。通过液相色谱-傅里叶变换质谱 (LC-FTMS) 对提取物 1290 进行化学分析,结果显示存在 29 种化合物,其中 8 种具有假定的结构匹配。总之,九种选定的抗感染药用植物中有五种在对人类角质形成细胞无害的浓度下对至少一种 MDR ESKAPE 病原体表现出生长抑制活性。此外,Z. armatum 被确定为群体猝灭天然产物的来源,并且值得对该物种进行进一步的生物测定指导分级分离。
Local people in the Sudhnoti district of Pakistan share a rich practice of traditional medicine for the treatment of a variety of ailments. We selected nine plants from the Sudhnoti ethnopharmacological tradition used for the treatment of infectious and inflammatory disease. Our aim was to evaluate the in vitro anti-infective potential of extracts from these species against multidrug-resistant (MDR) ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Plant specimens were collected in the Sudhnoti district of Pakistan and vouchers deposited in Pakistan and the USA. Dried bulk specimens were ground into a fine powder and extracted by aqueous decoction and maceration in ethanol. Extracts were assessed for growth inhibitory activity against ESKAPE pathogens and biofilm and quorum sensing activity was assessed in Staphylococcus aureus. Cytotoxicity to human cells was assessed via a lactate dehydrogenase assay of treated human keratinocytes (HaCaTs). Four ethanolic extracts (Zanthoxylum armatum, Adiantum capillus-venaris, Artemisia absinthium, and Martynia annua) inhibited the growth of MDR strains of ESKAPE pathogens (IC50: 256 μg mL−1). All extracts, with the exception of Pyrus pashia and M. annua, exhibited significant quorum quenching in a reporter strain for S. aureus agr I. The ethanolic extract of Z. armatum fruits (Extract 1290) inhibited quorum sensing (IC50 32–256 μg mL−1) in S. aureus reporter strains for agr I-III. The quorum quenching activity of extract 1290 was validated by detection of δ-toxin in the bacterial supernatant, with concentrations of 64–256 μg mL−1 sufficient to yield a significant drop in δ-toxin production. None of the extracts inhibited S. aureus biofilm formation at sub-inhibitory concentrations for growth. All extracts were well tolerated by human keratinocytes (LD50 ≥ 256 μg mL−1). Chemical analysis of extract 1290 by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) revealed the presence of 29 compounds, including eight with putative structural matches. In conclusion, five out of the nine selected anti-infective medicinal plants exhibited growth inhibitory activity against at least one MDR ESKAPE pathogen at concentrations not harmful to human keratinocytes. Furthermore, Z. armatum was identified as a source of quorum quenching natural products and further bioassay-guided fractionation of this species is merited.
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