Structural Insights into the Lipopolysaccharide Transport (Lpt) System as a Novel Antibiotic Target.

IF 3.3 4区 生物学 Q2 MICROBIOLOGY
Journal of Microbiology Pub Date : 2024-04-01 Epub Date: 2024-05-31 DOI:10.1007/s12275-024-00137-w
Yurim Yoon, Saemee Song
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引用次数: 0

Abstract

Lipopolysaccharide (LPS) is a critical component of the extracellular leaflet within the bacterial outer membrane, forming an effective physical barrier against environmental threats in Gram-negative bacteria. After LPS is synthesized and matured in the bacterial cytoplasm and the inner membrane (IM), LPS is inserted into the outer membrane (OM) through the ATP-driven LPS transport (Lpt) pathway, which is an energy-intensive process. A trans-envelope complex that contains seven Lpt proteins (LptA-LptG) is crucial for extracting LPS from the IM and transporting it across the periplasm to the OM. The last step in LPS transport involves the mediation of the LptDE complex, facilitating the insertion of LPS into the outer leaflet of the OM. As the Lpt system plays an essential role in maintaining the impermeability of the OM via LPS decoration, the interactions between these interconnected subunits, which are meticulously regulated, may be potential targets for the development of new antibiotics to combat multidrug-resistant Gram-negative bacteria. In this review, we aimed to provide an overview of current research concerning the structural interactions within the Lpt system and their implications to clarify the function and regulation of LPS transport in the overall process of OM biogenesis. Additionally, we explored studies on the development of therapeutic inhibitors of LPS transport, the factors that limit success, and future prospects.

Abstract Image

脂多糖转运(Lpt)系统作为新型抗生素靶点的结构洞察。
脂多糖(LPS)是细菌外膜胞外小叶的重要组成部分,在革兰氏阴性细菌中形成了抵御环境威胁的有效物理屏障。LPS 在细菌细胞质和内膜(IM)中合成并成熟后,通过 ATP 驱动的 LPS 转运(Lpt)途径插入外膜(OM),这是一个能量密集型过程。包含 7 个 Lpt 蛋白(LptA-LptG)的跨包膜复合体对于从内膜提取 LPS 并将其穿过包膜运送到外膜至关重要。LPS 运输的最后一步涉及 LptDE 复合物的调解,促进 LPS 插入 OM 的外叶。由于 Lpt 系统在通过 LPS 装饰维持 OM 的不可渗透性方面发挥着至关重要的作用,这些相互关联的亚基之间的相互作用受到严格调控,可能成为开发新抗生素以对抗多重耐药革兰氏阴性菌的潜在目标。在本综述中,我们旨在概述目前有关 Lpt 系统内部结构相互作用的研究及其对阐明 LPS 转运在整个 OM 生物发生过程中的功能和调控的影响。此外,我们还探讨了 LPS 转运治疗抑制剂的开发研究、限制成功的因素以及未来前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Microbiology
Journal of Microbiology 生物-微生物学
CiteScore
5.70
自引率
3.30%
发文量
0
审稿时长
3 months
期刊介绍: Publishes papers that deal with research on microorganisms, including archaea, bacteria, yeasts, fungi, microalgae, protozoa, and simple eukaryotic microorganisms. Topics considered for publication include Microbial Systematics, Evolutionary Microbiology, Microbial Ecology, Environmental Microbiology, Microbial Genetics, Genomics, Molecular Biology, Microbial Physiology, Biochemistry, Microbial Pathogenesis, Host-Microbe Interaction, Systems Microbiology, Synthetic Microbiology, Bioinformatics and Virology. Manuscripts dealing with simple identification of microorganism(s), cloning of a known gene and its expression in a microbial host, and clinical statistics will not be considered for publication by JM.
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