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表没食子儿茶素没食子酸酯对具有不同耐药表型的[具体对象]的表观遗传和药物反应调节

Epigenetic and Drug Response Modulation of Epigalocaten-In-3-Gallate in with Divergent Resistance Phenotypes.

作者信息

Mira Ana Rita, Zeferino Ana Sofia, Inácio Raquel, Delgadinho Mariana, Brito Miguel, Calado Cecília R C, Ribeiro Edna

机构信息

H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Av. D. João II, lote 4.69.01, Parque das Nações, 1990-096 Lisboa, Portugal.

Hospital do Espírito Santo de Évora, E.P.E., Largo do Sr. da Pobreza, 7000-811 Évora, Portugal.

出版信息

Antibiotics (Basel). 2023 Mar 4;12(3):519. doi: 10.3390/antibiotics12030519.

Abstract

Healthcare-associated methicillin-resistant infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. strains ( = 32) were isolated from infected patients in a Lisbon hospital. The identification of the resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria's molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of , and was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria's molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator , particularly in MRSA strains, as well as the key drug response modulators and . These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms.

摘要

医疗保健相关的耐甲氧西林感染在全球范围内呈现出极高的发病率和死亡率。我们旨在评估表没食子儿茶素-3-没食子酸酯(EGCG)与不同抗生素对具有不同耐药表型的菌株的抗菌潜力和协同作用。还评估了EGCG暴露对表观遗传和耐药关键调节因子的影响。从里斯本一家医院的感染患者中分离出32株菌株。通过自动化方法确定耐药表型。根据欧盟CAST指南,通过纸片扩散法进行抗生素协同试验,并同时暴露于EGCG(250、100、50和25μg/mL)。通过傅里叶变换红外光谱(FTIR)评估细菌的分子谱。使用qRT-PCR进行、和的转录表达分析。FTIR光谱分析能够清晰地区分耐甲氧西林金黄色葡萄球菌/甲氧西林敏感金黄色葡萄球菌(MRSA/MSSA)菌株以及EGCG暴露对细菌分子谱的影响。不同的耐药表型与表观遗传调节因子的不同转录表达相关,特别是在MRSA菌株中,以及关键药物反应调节因子和。这些结果清楚地表明,EGCG暴露改变了关键表观遗传和药物反应基因的表达模式,并伴有不同的耐药谱,这支持了其在抗微生物治疗和/或针对耐药微生物的治疗佐剂方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c87/10044528/7ba2a87d1da6/antibiotics-12-00519-g001.jpg

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