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姜黄素对浮游细胞和生物膜中抗耐甲氧西林金黄色葡萄球菌的活性及可能作用机制的研究。

Anti-MRSA activity of curcumin in planktonic cells and biofilms and determination of possible action mechanisms.

机构信息

School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil.

School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.

出版信息

Microb Pathog. 2021 Jun;155:104892. doi: 10.1016/j.micpath.2021.104892. Epub 2021 Apr 21.

Abstract

Staphylococcus aureus is a commensal bacterium and opportunistic human pathogen that can cause a wide variety of clinical infections. It is recognized for its ability to acquire antimicrobial resistance, so methicillin-resistant Staphylococcus aureus (MRSA) infections are a global healthcare challenge. Therefore, the development of new therapeutic options and alternative therapies for treatment is necessary. Curcumin, a polyphenolic substance found in the rhizome of turmeric longa L, has been shown to have several therapeutic properties, including antimicrobial activity. The objective of the study was to evaluate the in vitro antibacterial activity of curcumin alone and associated with oxacillin against MRSA strains, to analyze the mechanism of cell death involved in the isolated action of curcumin by means of flow cytometry and molecular docking, and to verify its superbiofilm action. Curcumin showed antibacterial activity in the range of 125-500 μg/mL against the tested strains, since it caused an increase in membrane permeability and DNA fragmentation, as revealed by flow cytometry analysis. Moreover, it was possible to observe interactions of curcumin with wild-type S. aureus DHFR, S. aureus gyrase and S. aureus gyrase complex with DNA, DNA (5'-D(CPGPAPTPGPCP*G)-3') and Acyl-PBP2a from MRSA by molecular docking. Curcumin also had a synergistic and additive effect when associated with oxacillin, and significantly reduced the cell viability of the analyzed biofilms. Thus, curcumin is a possible candidate for pharmaceutical formulation development for the treatment of MRSA infections.

摘要

金黄色葡萄球菌是一种共生细菌和机会性人类病原体,可引起多种临床感染。它以获得抗微生物耐药性的能力而闻名,因此耐甲氧西林金黄色葡萄球菌(MRSA)感染是全球医疗保健面临的挑战。因此,有必要开发新的治疗选择和替代疗法。姜黄素是姜黄根茎中的一种多酚物质,已被证明具有多种治疗特性,包括抗菌活性。本研究的目的是评估姜黄素单独和与苯唑西林联合对 MRSA 菌株的体外抗菌活性,通过流式细胞术和分子对接分析姜黄素的分离作用所涉及的细胞死亡机制,并验证其对超级生物膜的作用。姜黄素对测试菌株的抗菌活性范围为 125-500μg/ml,因为它通过流式细胞术分析显示出增加膜通透性和 DNA 片段化。此外,通过分子对接观察到姜黄素与野生型金黄色葡萄球菌 DHFR、金黄色葡萄球菌拓扑异构酶和金黄色葡萄球菌拓扑异构酶-DNA 复合物、DNA(5'-D(CPGPAPTPGPCP*G)-3')和来自 MRSA 的 Acyl-PBP2a 的相互作用。姜黄素与苯唑西林联合使用时也具有协同和相加作用,并显著降低了分析生物膜的细胞活力。因此,姜黄素是开发用于治疗 MRSA 感染的药物制剂的候选药物。

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