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细菌外排泵蛋白在跨微生物物种抗生素耐药性中的作用。

Role of bacterial efflux pump proteins in antibiotic resistance across microbial species.

作者信息

Kumawat Manoj, Nabi Bilkees, Daswani Muskan, Viquar Iqra, Pal Namrata, Sharma Poonam, Tiwari Shikha, Sarma Devojit Kumar, Shubham Swasti, Kumar Manoj

机构信息

Department of Microbiology, ICMR- National Institute for Research in Environmental Health, Bhopal, 462030, India.

Department of Biochemistry & Biochemical Engineering, SHUATS, Allahabad, 211007, India.

出版信息

Microb Pathog. 2023 Aug;181:106182. doi: 10.1016/j.micpath.2023.106182. Epub 2023 May 30.

Abstract

Efflux proteins are transporter molecules that actively pump out a variety of substrates, including antibiotics, from cells to the environment. They are found in both Gram-positive and Gram-negative bacteria and eukaryotic cells. Based on their protein sequence homology, energy source, and overall structure, efflux proteins can be divided into seven groups. Multidrug efflux pumps are transmembrane proteins produced by microbes to enhance their survival in harsh environments and contribute to antibiotic resistance. These pumps are present in all bacterial genomes studied, indicating their ancestral origins. Many bacterial genes encoding efflux pumps are involved in transport, a significant contributor to antibiotic resistance in microbes. Efflux pumps are widely implicated in the extrusion of clinically relevant antibiotics from cells to the extracellular environment and, as such, represent a significant challenge to antimicrobial therapy. This review aims to provide an overview of the structures and mechanisms of action, substrate profiles, regulation, and possible inhibition of clinically relevant efflux pumps. Additionally, recent advances in research and the pharmacological exploitation of efflux pump inhibitors as a promising intervention for combating drug resistance will be discussed.

摘要

外排蛋白是一类转运分子,能够将包括抗生素在内的多种底物从细胞主动泵出到细胞外环境。它们存在于革兰氏阳性菌、革兰氏阴性菌以及真核细胞中。根据其蛋白质序列同源性、能量来源和整体结构,外排蛋白可分为七组。多药外排泵是微生物产生的跨膜蛋白,可增强其在恶劣环境中的生存能力,并导致抗生素耐药性。这些泵存在于所有已研究的细菌基因组中,表明它们具有共同的起源。许多编码外排泵的细菌基因都参与转运过程,这是微生物抗生素耐药性的一个重要因素。外排泵广泛参与将临床相关抗生素从细胞内排到细胞外环境的过程,因此,这对抗菌治疗构成了重大挑战。本综述旨在概述临床相关外排泵的结构、作用机制、底物谱、调控以及可能的抑制方式。此外,还将讨论外排泵抑制剂研究的最新进展以及将其作为对抗耐药性的一种有前景的干预措施的药理学应用。

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