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酚类化合物对自诱导物的调节作用作为细菌潜在的抗毒力靶点

Autoinducers modulation as a potential anti-virulence target of bacteria by phenolic compounds.

作者信息

Moreno-Chamba Bryan, Salazar-Bermeo Julio, Navarro-Simarro Pablo, Narváez-Asensio Marta, Martínez-Madrid María Concepción, Saura Domingo, Martí Nuria, Valero Manuel

机构信息

Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández de Elche (UMH), Alicante, Spain; Instituto de Ingeniería de Alimentos para el Desarrollo, Universitat Politècnica de València, Valencia, Spain.

Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández de Elche (UMH), Alicante, Spain.

出版信息

Int J Antimicrob Agents. 2023 Oct;62(4):106937. doi: 10.1016/j.ijantimicag.2023.106937. Epub 2023 Jul 28.

Abstract

OBJECTIVE

The goal of this study was to determine the effects of phenolic extracts from grape (GrPE), pomegranate (PoPE), and persimmon (PePE) by-products on bacterial virulence activities such as biofilms, motility, energy-dependent efflux pumps, and β-lactamase activity, which are modulated primarily by quorum sensing (QS), defining their potential applications.

METHOD

The microdilution method was used to determine the minimum inhibitory concentration (MIC) and sub-inhibitory concentrations (SICs) of the extracts against reference pathogenic bacteria. The antibacterial mode of action was determined by labelling bacterial cells in in vivo cell-tracking experiments.

RESULTS

Antibiograms showed that PoPE inhibited bacteria at lower concentrations, and PePE had a stronger effect against Klebsiella pneumoniae. Both extracts caused significant cell membrane damage (CMD), whereas GrPE did not. At SICs, all extracts showed anti-QS activity, especially PePE, which inhibited violacein and pyocyanin production at 1/128 × MIC. Additionally, QS autoinducers found in Chromobacterium violaceum and Pseudomonas aeruginosa were modulated by the extracts; PePE showed the highest modulation. Antibiofilm assays revealed that GrPE, at MIC and 2 × MIC, acted as a potent antibiofilm agent against biofilms of Pseudomonas putida, Bacillus cereus, and Staphylococcus aureus, which was related to disruption of swarming motility by GrPE. All extracts, especially PoPE, exerted a potent effect against the activation of efflux pumps of P. aeruginosa as well as β-lactamase activity in K. pneumoniae.

CONCLUSION

Results suggest that the anti-virulence potential of the extracts may be related to their effect as extracellular autoinducer modulators. This study allowed to define potential applications of these extracts.

摘要

目的

本研究的目的是确定葡萄(GrPE)、石榴(PoPE)和柿子(PePE)副产品中的酚类提取物对细菌毒力活性的影响,如生物膜、运动性、能量依赖性外排泵和β-内酰胺酶活性,这些活性主要由群体感应(QS)调节,从而确定它们的潜在应用。

方法

采用微量稀释法测定提取物对参考病原菌的最低抑菌浓度(MIC)和亚抑菌浓度(SICs)。通过体内细胞追踪实验标记细菌细胞来确定抗菌作用模式。

结果

抗菌谱显示,PoPE在较低浓度下就能抑制细菌,而PePE对肺炎克雷伯菌的作用更强。两种提取物均导致显著的细胞膜损伤(CMD),而GrPE没有。在亚抑菌浓度下,所有提取物均表现出抗群体感应活性,尤其是PePE,在1/128×MIC时能抑制紫色杆菌素和绿脓菌素的产生。此外,提取物还调节了紫色色杆菌和铜绿假单胞菌中的群体感应自诱导物;PePE表现出最高的调节作用。抗生物膜试验表明,GrPE在MIC和2×MIC时,对恶臭假单胞菌、蜡样芽孢杆菌和金黄色葡萄球菌的生物膜具有强大的抗生物膜作用,这与GrPE破坏群体运动性有关。所有提取物,尤其是PoPE,对铜绿假单胞菌外排泵的激活以及肺炎克雷伯菌中的β-内酰胺酶活性都有强大的抑制作用。

结论

结果表明,提取物的抗毒力潜力可能与其作为细胞外自诱导物调节剂的作用有关。本研究确定了这些提取物的潜在应用。

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