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微阵列分析丁香酚对耐甲氧西林金黄色葡萄球菌基因组效应

Microarray Analysis of the Genomic Effect of Eugenol on Methicillin-Resistant .

机构信息

Department of Medical Laboratory Science, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Ekiti State, Nigeria.

Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.

出版信息

Molecules. 2022 May 19;27(10):3249. doi: 10.3390/molecules27103249.

DOI:10.3390/molecules27103249
PMID:35630724
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9147492/
Abstract

is a highly adaptive human pathogen responsible for serious hospital- and community-acquired infectious diseases, ranging from skin and soft tissue infections, to complicated and life-threatening conditions such as endocarditis and toxic shock syndrome (TSS). The rapid development of resistance of this organism to available antibiotics over the last few decades has necessitated a constant search for more efficacious antibacterial agents. Eugenol (4-allyl-2-methoxyphenol) belongs to the class of chemical compounds called phenylpropanoids. It is a pure-to-pale yellow, oily liquid substance, mostly extracted as an essential oil from natural products such as clove, cinnamon, nutmeg, basil, and bay leaf. Eugenol has previously been shown to have antimicrobial activity against methicillin-resistant (MRSA). However, the mechanism of action of eugenol against MRSA has not, as yet, been elucidated; hence, the necessity of this study. Global gene expression patterns in response to challenge from subinhibitory concentrations of eugenol were analysed using the Agilent DNA microarray system to identify genes that can be used as drug targets-most importantly, essential genes involved in unique metabolic pathways elicited for bacterial survival. Transcriptomic analysis of fluctuating genes revealed those involved in amino acid metabolism, fatty acid metabolism, translational, and ribosomal pathways. In amino acid metabolism, for instance, the gene encodes for -acetyl-gamma-glutamyl-phosphate reductase. The gene plays an important role in the biosynthesis of arginine from glutamate in the amino acid metabolic pathway. It is the enzyme that catalyses the third step in the latter reaction, and without this process the production of -acetylglutamate 5-semialdehyde cannot be completed from the NADP-dependent reduction of -acetyl-5-glutamyl phosphate, which is essential for the survival of some microorganisms and plants. This study enables us to examine complete global transcriptomic responses in MRSA when challenged with eugenol. It reveals novel information with the potential to further benefit the exploratory quest for novel targets against this pathogen, with a view to the development of efficacious antimicrobial agents for the treatment of associated infections.

摘要

金黄色葡萄球菌是一种高度适应人体的病原体,可导致严重的医院和社区获得性感染,包括皮肤和软组织感染,以及感染性心内膜炎和中毒性休克综合征 (TSS) 等复杂且危及生命的疾病。在过去几十年中,该生物体对现有抗生素的耐药性迅速发展,因此需要不断寻找更有效的抗菌剂。丁香酚(4-丙烯基-2-甲氧基苯酚)属于称为苯丙素的化合物类别。它是一种纯至淡黄色油性液体物质,主要从丁香、肉桂、肉豆蔻、罗勒和月桂叶等天然产物中提取为精油。丁香酚先前已显示对耐甲氧西林金黄色葡萄球菌 (MRSA) 具有抗菌活性。然而,丁香酚对 MRSA 的作用机制尚未阐明;因此,需要进行这项研究。使用安捷伦 DNA 微阵列系统分析金黄色葡萄球菌对亚抑菌浓度丁香酚的反应的全基因表达模式,以鉴定可作为药物靶点的基因,最重要的是,涉及细菌生存所需独特代谢途径的必需基因。波动基因的转录组分析揭示了参与氨基酸代谢、脂肪酸代谢、翻译和核糖体途径的基因。例如,在氨基酸代谢中, 基因编码 -乙酰基-γ-谷氨酰磷酸还原酶。 基因在从谷氨酸生物合成精氨酸的氨基酸代谢途径中起着重要作用。它是催化后一反应第三步的酶,没有这个过程,就不能完成从 NADP 依赖性还原 -乙酰-5-谷氨酰磷酸到 -乙酰谷氨酸 5-半醛的反应,而后者对于某些微生物和植物的生存是必需的。这项研究使我们能够在金黄色葡萄球菌受到丁香酚挑战时检查其完整的全基因组转录组反应。它揭示了具有潜在潜力的新信息,可以进一步促进针对该病原体的新型靶点的探索性研究,以期开发出有效的抗菌剂来治疗相关感染。

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