Lupeol as a Potential Inhibitor of NorA Efflux Pumps in Staphylococcus aureus: In Silico and In Vitro Evidence.

IF 2.5 4区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Nara Juliana Santos Araújo, Camila Aparecida Pereira Silva, Vanessa Lima Bezerra, Cicera Datiane Morais Oliveira-Tintino, Gabriel Gonçalves de Alencar, Maria do Socorro Costa, Ana Raquel Pereira da Silva, Josefa Sayonara Dos Santos, Kamila Correa Camara, Heberty diTarso Fernandes Facundo, Lívia Pereira Ferreira, Henrique Douglas Melo Coutinho, José Maria Barbosa Filho, Carolina Bandeira Domiciano, José Bezerra de Araújo-Neto, Jacqueline Cosmo Andrade-Pinheiro
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引用次数: 0

Abstract

Antimicrobial resistance remains one of the major challenges to global public health, compromising the effectiveness of treatments and contributing to increased morbidity and mortality associated with bacterial infections. Among the mechanisms involved, efflux pumps-such as NorA, expressed in resistant strains of Staphylococcus aureus-are particularly noteworthy. These transport proteins actively expel antibiotics from the cell, reducing their intracellular concentration. In this context, natural compounds have been explored as potential resistance inhibitors, with a focus on the triterpene lupeol, known for its pharmacological properties. This study evaluates the activity of lupeol against the NorA efflux pump using in vitro assays and in silico modeling. The minimum inhibitory concentration (MIC) is determined by broth microdilution, and pump inhibition is assessed via ethidium bromide-induced fluorescence. SYTOX Green assays indicated that lupeol does not compromise bacterial membrane integrity. Although lupeol presented a MIC ≥ 1024 μg mL-1, it demonstrates significant inhibition of NorA activity. Molecular docking reveals a binding energy of -7.112 kcal mol-1 and interactions with key residues of the protein, outperforming the CCCP control. These findings suggest that lupeol acts as a modulator of bacterial resistance, with potential application as a therapeutic adjuvant in the treatment of infections caused by multidrug-resistant S. aureus.

Lupeol作为金黄色葡萄球菌NorA外排泵的潜在抑制剂:体内和体外证据。
抗微生物药物耐药性仍然是全球公共卫生面临的主要挑战之一,影响治疗的有效性,并导致与细菌感染相关的发病率和死亡率增加。在所涉及的机制中,外排泵——如在金黄色葡萄球菌耐药菌株中表达的NorA——特别值得注意。这些转运蛋白积极地将抗生素从细胞中排出,降低其在细胞内的浓度。在这种情况下,天然化合物已被探索作为潜在的耐药抑制剂,重点是三萜芦皮醇,以其药理特性而闻名。本研究通过体外实验和计算机模拟来评估芦皮醇对NorA外排泵的活性。最小抑制浓度(MIC)是通过肉汤微量稀释测定的,泵抑制是通过溴化乙啶诱导荧光评估的。SYTOX Green试验表明lupeol不会损害细菌膜的完整性。虽然芦皮酮的MIC≥1024 μ mL-1,但对NorA活性有明显的抑制作用。分子对接显示结合能为-7.112 kcal mol-1,并与蛋白质的关键残基相互作用,优于CCCP对照。这些发现表明,lupeol可作为细菌耐药调节剂,在治疗耐多药金黄色葡萄球菌引起的感染方面具有潜在的辅助治疗应用价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ChemistryOpen
ChemistryOpen CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
4.80
自引率
4.30%
发文量
143
审稿时长
1 months
期刊介绍: ChemistryOpen is a multidisciplinary, gold-road open-access, international forum for the publication of outstanding Reviews, Full Papers, and Communications from all areas of chemistry and related fields. It is co-owned by 16 continental European Chemical Societies, who have banded together in the alliance called ChemPubSoc Europe for the purpose of publishing high-quality journals in the field of chemistry and its border disciplines. As some of the governments of the countries represented in ChemPubSoc Europe have strongly recommended that the research conducted with their funding is freely accessible for all readers (Open Access), ChemPubSoc Europe was concerned that no journal for which the ethical standards were monitored by a chemical society was available for such papers. ChemistryOpen fills this gap.
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