Bacterial effluxome as a barrier against antimicrobial agents: structural biology aspects and drug targeting.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Tissue Barriers Pub Date : 2022-10-02 DOI:10.1080/21688370.2021.2013695

Pownraj Brindangnanam, Ajit Ramesh Sawant, K Prashanth, Mohane Selvaraj Coumar

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引用次数: 3

Abstract

Antimicrobial resistance (AMR) is fast becoming a medical crisis affecting the entire global population. The bacterial membrane is the first layer of defense for the bacteria against antimicrobial agents (AMA), specifically transporters in the membrane efflux these AMA out of the bacteria and plays a significant role in the AMR development. Understanding the structure and the functions of these efflux transporters is essential to overcome AMR. This review discusses efflux transporters (primary, secondary, and tripartite), their domain architectures, substrate specificities, and efflux pump inhibitors (EPI). Special emphasis on nosocomial ESKAPEE (Enterococcus faecium., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli) pathogens, their multidrug efflux targets and inhibitors are discussed. Deep knowledge about the functioning of efflux pumps and their structural aspects will open up opportunities for developing new EPI, which could be used along with AMA as combination therapy to overcome the emerging AMR crisis.

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细菌排出体作为抗微生物药物的屏障:结构生物学方面和药物靶向。

抗菌素耐药性(AMR)正迅速成为影响全球人口的医疗危机。细菌膜是细菌对抗抗菌剂(AMA)的第一层防御，特别是膜上的转运体将这些AMA排出细菌，在抗菌剂耐药性的发展中起着重要作用。了解这些外排转运体的结构和功能对克服抗菌素耐药性至关重要。本文综述了外排转运蛋白(一级转运蛋白、二级转运蛋白和三方转运蛋白)、它们的结构域结构、底物特异性和外排泵抑制剂(EPI)。特别强调医院的ESKAPEE(屎肠球菌)。讨论了金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌、肠杆菌和大肠杆菌等病原菌及其多药外排靶点和抑制剂。对外排泵功能及其结构方面的深入了解将为开发新的EPI提供机会，它可以与AMA一起作为联合疗法来克服正在出现的AMR危机。

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来源期刊

Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.60

自引率

6.50%

发文量

期刊介绍： Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.