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熊果酸对……抗菌活性的作用机制基础评估

Evaluation of the mechanistic basis for the antibacterial activity of ursolic acid against .

作者信息

Liu Guanhui, Qin Peng, Cheng Xinying, Wu Lifei, Zhao Wentao, Gao Wei

机构信息

School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan, China.

Chenguang Biotechnology Group Handan Co., Ltd., Handan, China.

出版信息

Front Microbiol. 2024 May 17;15:1389242. doi: 10.3389/fmicb.2024.1389242. eCollection 2024.

DOI:10.3389/fmicb.2024.1389242
PMID:38827151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11140147/
Abstract

The antibiotics are generally regarded as the first choice approach to treat dairy mastitis, targeting the public health problems associated with the food safety and the emergence of antibioticresistant bacteria. The objective of the study was to evaluate the antibacterial efficacy of ursolic acid (UA) when used to treat and other isolates associated with bovine mastitis and to clarify the mechanistic basis for these effects. The bacteriostatic properties of UA extracted from L. at four different purity levels were assessed by calculating minimum inhibitory concentration (MIC) values, while the synergistic effects of combining 98% UA with antibiotics were evaluated by measuring the fractional inhibitory concentration index (FICI). Changes in biofilm formation and the growth curves of the clinical isolates were assessed to clarify the bacteriostatic effect of UA. Furthermore, the cell wall integrity, protein synthesis, and reactive oxygen species (ROS) production were assessed to determine the antibacterial mechanism of UA treatment. Ultimately, UA was revealed to exhibit robust activity against Gram-positive bacteria including (ATCC 25923), (ATCC27957), (ATCC13813), (ATCC29212), and (ATCC25175). However, it did not affect (ATCC 25922). The MIC values of UA preparations that were 98, 50, 30, and 10% pure against were 39, 312, 625, and 625 μg/mL, respectively, whereas the corresponding MIC for was >5,000 μg/mL. The minimum bactericidal concentrations of 98% UA when used to treat three clinical isolates (S4, S5, and S6) were 78, 78, and 156 μg/mL, respectively. Levels of biofilm formation for clinical isolates decreased with increasing 98% UA concentrations. Above the MIC dose, UA treatment resulted in the dissolution of bacterial cell walls and membranes, with cells becoming irregularly shaped and exhibiting markedly impaired intracellular protein synthesis. treated with 98% UA was able to rapidly promote intracellular ROS biogenesis. Together, these data highlight the promising utility of UA as a compound that can be used together with other antibiotics for the treatment of infections caused by .

摘要

抗生素通常被视为治疗奶牛乳腺炎的首选方法,旨在解决与食品安全及抗生素耐药菌出现相关的公共卫生问题。本研究的目的是评估熊果酸(UA)用于治疗与牛乳腺炎相关的其他分离株时的抗菌效果,并阐明这些作用的机制基础。通过计算最低抑菌浓度(MIC)值来评估从委陵菜中提取的四种不同纯度水平的UA的抑菌特性,同时通过测量分数抑菌浓度指数(FICI)来评估98%UA与抗生素联合使用的协同效应。评估生物膜形成和临床分离株生长曲线的变化以阐明UA的抑菌作用。此外,评估细胞壁完整性、蛋白质合成和活性氧(ROS)产生以确定UA治疗的抗菌机制。最终发现,UA对革兰氏阳性菌包括金黄色葡萄球菌(ATCC 25923)、表皮葡萄球菌(ATCC27957)、停乳链球菌(ATCC13813)、无乳链球菌(ATCC29212)和乳房链球菌(ATCC25175)表现出强大的活性。然而,它对大肠杆菌(ATCC 25922)没有影响。纯度为98%、50%、30%和10%的UA制剂对金黄色葡萄球菌的MIC值分别为39、312、625和625μg/mL,而对大肠杆菌的相应MIC>5000μg/mL。98%UA用于治疗三株临床金黄色葡萄球菌分离株(S4、S5和S6)时的最低杀菌浓度分别为78、78和156μg/mL。临床金黄色葡萄球菌分离株的生物膜形成水平随着98%UA浓度的增加而降低。在MIC剂量以上,UA处理导致细菌细胞壁和细胞膜溶解,细胞形状变得不规则,细胞内蛋白质合成明显受损。用98%UA处理能够迅速促进细胞内ROS的生物合成。总之,这些数据突出了UA作为一种可与其他抗生素联合用于治疗由金黄色葡萄球菌引起的感染的化合物的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/eb02ef7b3c1b/fmicb-15-1389242-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/6971838ac87e/fmicb-15-1389242-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/2542f7a88bb6/fmicb-15-1389242-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/ec6fc1c49f9d/fmicb-15-1389242-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/b049c141d9f6/fmicb-15-1389242-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/eb02ef7b3c1b/fmicb-15-1389242-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/6971838ac87e/fmicb-15-1389242-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/2542f7a88bb6/fmicb-15-1389242-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/ec6fc1c49f9d/fmicb-15-1389242-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/b049c141d9f6/fmicb-15-1389242-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c2b/11140147/eb02ef7b3c1b/fmicb-15-1389242-g005.jpg

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