耐药性结节分化(RND)外排泵转运体的结构和功能多样性及其对抗菌药耐药性的影响。

IF 8 1区 生物学 Q1 MICROBIOLOGY Microbiology and Molecular Biology Reviews Pub Date : 2024-09-26 Epub Date: 2024-09-05 DOI:10.1128/mmbr.00089-23
Logan G Kavanaugh, Debayan Dey, William M Shafer, Graeme L Conn
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引用次数: 0

摘要

摘要 细菌外排泵的发现极大地推动了我们对细菌如何抵抗其所遇到的细胞毒性化合物的认识。在结构和功能各异的外排泵家族中,抗性-结节-分裂(RND)超家族的外排泵因能降低结构各异的抗菌素的细胞内浓度而引人注目。许多革兰氏阴性细菌都拥有 RND 系统,其中包括那些导致严重人类疾病的细菌,并且经常导致对多种抗生素产生耐药性。在此,我们回顾了目前有关临床上重要病原体的三方 RND 外排泵代表性转运蛋白的结构-功能关系的文献。我们强调了它们对细菌耐受临床使用的抗生素、宿主防御抗菌素和其他杀菌剂的贡献,并着重介绍了帮助细菌在抗菌素面前生存的外排转运体之间的结构异同。此外,我们还讨论了促进和推动外排泵研究的技术进步,并提出了将推动抗菌药开发工作的未来研究领域。
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Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.

SUMMARYThe discovery of bacterial efflux pumps significantly advanced our understanding of how bacteria can resist cytotoxic compounds that they encounter. Within the structurally and functionally distinct families of efflux pumps, those of the Resistance-Nodulation-Division (RND) superfamily are noteworthy for their ability to reduce the intracellular concentration of structurally diverse antimicrobials. RND systems are possessed by many Gram-negative bacteria, including those causing serious human disease, and frequently contribute to resistance to multiple antibiotics. Herein, we review the current literature on the structure-function relationships of representative transporter proteins of tripartite RND efflux pumps of clinically important pathogens. We emphasize their contribution to bacterial resistance to clinically used antibiotics, host defense antimicrobials and other biocides, as well as highlighting structural similarities and differences among efflux transporters that help bacteria survive in the face of antimicrobials. Furthermore, we discuss technical advances that have facilitated and advanced efflux pump research and suggest future areas of investigation that will advance antimicrobial development efforts.

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来源期刊
CiteScore
18.80
自引率
0.80%
发文量
27
期刊介绍: Microbiology and Molecular Biology Reviews (MMBR), a journal that explores the significance and interrelationships of recent discoveries in various microbiology fields, publishes review articles that help both specialists and nonspecialists understand and apply the latest findings in their own research. MMBR covers a wide range of topics in microbiology, including microbial ecology, evolution, parasitology, biotechnology, and immunology. The journal caters to scientists with diverse interests in all areas of microbial science and encompasses viruses, bacteria, archaea, fungi, unicellular eukaryotes, and microbial parasites. MMBR primarily publishes authoritative and critical reviews that push the boundaries of knowledge, appealing to both specialists and generalists. The journal often includes descriptive figures and tables to enhance understanding. Indexed/Abstracted in various databases such as Agricola, BIOSIS Previews, CAB Abstracts, Cambridge Scientific Abstracts, Chemical Abstracts Service, Current Contents- Life Sciences, EMBASE, Food Science and Technology Abstracts, Illustrata, MEDLINE, Science Citation Index Expanded (Web of Science), Summon, and Scopus, among others.
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