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解析 对人类健康的影响,以及探索天然化合物作为外排泵抑制剂来治疗多药耐药性。

Deciphering the impact of on human health, and exploration of natural compounds as efflux pump inhibitors to treat multidrug resistance.

机构信息

Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore 641043, Tamil Nadu, India.

Department of Pharmacology and Toxicology, School of Pharmacy, King Khalid University, Abha 652529, Saudi Arabia.

出版信息

J Med Microbiol. 2024 Aug;73(8). doi: 10.1099/jmm.0.001867.

Abstract

is an ESKAPE pathogen and threatens human health by generating infections with high fatality rates. leads to a spectrum of infections such as skin and wound infections, endocarditis, meningitis pneumonia, septicaemia and urinary tract infections. Recently, strains of have emerged as multidrug-resistant (MDR), meaning they are resistant to at least three different classes of antibiotics. MDR development is primarily intensified by widespread antibiotic misuse and inadequate stewardship. The World Health Organization (WHO) declared a precarious MDR species. maintains the MDR phenotype via a diverse array of antimicrobial metabolite-hydrolysing enzymes, efflux of antibiotics, impermeability and antibiotic target modification, thereby complicating treatment. Hence, a deeper understanding of the resistance mechanisms employed by MDR can give possible approaches to treat antimicrobial resistance. Resistance-nodulation-cell division (RND) efflux pumps have been identified as the key contributors to MDR determinants, owing to their capacity to force a broad spectrum of chemical substances out of the bacterial cell. Though synthetic inhibitors have been reported previously, their efficacy and safety are of debate. As resistance-modifying agents, phytochemicals are ideal choices. These natural compounds could eliminate the bacteria or interact with pathogenicity events and reduce the bacteria's ability to evolve resistance. This review aims to highlight the mechanism behind the multidrug resistance in and elucidate the utility of natural compounds as efflux pump inhibitors to deal with the infections caused by .

摘要

是 ESKAPE 病原体之一,通过引起高死亡率的感染威胁人类健康。 可导致多种感染,如皮肤和伤口感染、心内膜炎、脑膜炎、肺炎、败血症和尿路感染。最近, 菌株已成为多药耐药(MDR),这意味着它们至少对三种不同类别的抗生素具有耐药性。MDR 的发展主要是由于抗生素的广泛滥用和管理不善而加剧的。世界卫生组织(WHO)宣布 为一种不稳定的 MDR 物种。 通过多种抗菌代谢物水解酶、抗生素外排、不透性和抗生素靶标修饰来维持 MDR 表型,从而使治疗变得复杂。因此,深入了解 MDR 所采用的耐药机制可以为治疗抗菌药物耐药性提供可能的方法。抗性调节细胞分裂(RND)外排泵已被确定为 MDR 决定因素的主要贡献者,因为它们能够将广谱化学物质从细菌细胞中排出。尽管以前已经报道了合成抑制剂,但它们的疗效和安全性仍存在争议。作为耐药修饰剂,植物化学物质是理想的选择。这些天然化合物可以消除细菌或与致病性事件相互作用,降低细菌产生耐药性的能力。本综述旨在强调 中多药耐药的机制,并阐明天然化合物作为外排泵抑制剂在处理 引起的感染方面的应用。

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