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表没食子儿茶素没食子酸酯对金黄色葡萄球菌的耐药性和表观遗传调节潜力。

Drug Resistance and Epigenetic Modulatory Potential of Epigallocatechin-3-Gallate Against Staphylococcus aureus.

机构信息

Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096, Lisbon, Portugal.

Centro Hospitalar de Lisboa Central; Hospital Curry Cabral, Rua Beneficência, 8, 1050-099, Lisbon, Portugal.

出版信息

Curr Microbiol. 2022 Apr 9;79(5):149. doi: 10.1007/s00284-022-02841-5.

DOI:10.1007/s00284-022-02841-5
PMID:35397072
Abstract

Antimicrobial resistance of human pathogens, such as methicillin-resistant Staphylococcus aureus, is described by the World Health Organization as a health global challenge and efforts must be made for the discovery of new effective and safe compounds. This work aims to evaluate epigallocatechin-3-gallate (EGCG) epigenetic and modulatory drug potential against S. aureus in vitro and in vivo. S. aureus strains were isolated from commensal flora of healthy volunteers. Antibiotic susceptibility and synergistic assay were assessed through disk diffusion accordingly to EUCAST guidelines with and without co-exposure to EGCG at final concentrations of 250 µg/ml, 100 µg/ml, 50 µg/ml, and 25 µg/ml. Transcriptional expression of orfx, spdC, and WalKR was performed through qRT-PCR. A 90-day interventional study was performed with daily consumption of 225 mg of EGCG. Obtained data revealed a high prevalence of S. aureus colonization in healthcare workers and clearly demonstrated the antimicrobial and synergistic potential of EGCG as well as divergent resistant phenotypes associated with altered transcriptional expression of epigenetic and drug response modulators genes. Here, we demonstrate the potential of EGCG for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms and report divergent patterns of epigenetic modulators expression associated with phenotypic resistance profiles.

摘要

人病原体的抗微生物耐药性,如耐甲氧西林金黄色葡萄球菌,被世界卫生组织描述为全球健康挑战,必须努力发现新的有效和安全的化合物。这项工作旨在评估表没食子儿茶素没食子酸酯 (EGCG) 在体外和体内对金黄色葡萄球菌的表观遗传和调节药物潜力。金黄色葡萄球菌株从健康志愿者的共生菌群中分离出来。根据 EUCAST 指南,通过圆盘扩散评估抗生素敏感性和协同作用,同时在最终浓度为 250μg/ml、100μg/ml、50μg/ml 和 25μg/ml 时与 EGCG 共同暴露。通过 qRT-PCR 进行 orfx、spdC 和 WalKR 的转录表达。进行了为期 90 天的干预研究,每天摄入 225mg 的 EGCG。研究结果显示,医护人员中金黄色葡萄球菌定植的患病率很高,这清楚地表明了 EGCG 的抗菌和协同潜力,以及与表观遗传和药物反应调节剂基因转录表达改变相关的不同耐药表型。在这里,我们证明了 EGCG 作为对抗生素耐药微生物的抗菌治疗和/或治疗佐剂的潜力,并报告了与表型耐药谱相关的表观遗传调节剂表达的不同模式。

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