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针对细菌分泌途径的抗生素

Antibiotic targeting of the bacterial secretory pathway.

作者信息

Rao C V Smitha, De Waelheyns Evelien, Economou Anastassios, Anné Jozef

机构信息

Laboratory of Molecular Bacteriology, Rega Institute, Department of Microbiology and Immunology, KU Leuven, O&N1, 6th floor, Herestraat 49, P.O. Box 1037, B-3000 Leuven, Belgium.

Laboratory of Molecular Bacteriology, Rega Institute, Department of Microbiology and Immunology, KU Leuven, O&N1, 6th floor, Herestraat 49, P.O. Box 1037, B-3000 Leuven, Belgium; Institute of Molecular Biology and Biotechnology, FORTH, University of Crete, P.O. Box 1385, GR-711 10 Iraklio, Crete, Greece; Department of Biology, University of Crete, P.O. Box 1385, GR-71110 Iraklio, Crete, Greece.

出版信息

Biochim Biophys Acta. 2014 Aug;1843(8):1762-83. doi: 10.1016/j.bbamcr.2014.02.004. Epub 2014 Feb 15.

Abstract

Finding new, effective antibiotics is a challenging research area driven by novel approaches required to tackle unconventional targets. In this review we focus on the bacterial protein secretion pathway as a target for eliminating or disarming pathogens. We discuss the latest developments in targeting the Sec-pathway for novel antibiotics focusing on two key components: SecA, the ATP-driven motor protein responsible for driving preproteins across the cytoplasmic membrane and the Type I signal peptidase that is responsible for the removal of the signal peptide allowing the release of the mature protein from the membrane. We take a bird's-eye view of other potential targets in the Sec-pathway as well as other Sec-dependent or Sec-independent protein secretion pathways as targets for the development of novel antibiotics. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.

摘要

寻找新型、有效的抗生素是一个具有挑战性的研究领域,需要采用新方法来攻克非常规靶点。在本综述中,我们聚焦于细菌蛋白质分泌途径,将其作为消除病原体或使其失去活性的靶点。我们讨论了针对Sec途径开发新型抗生素的最新进展,重点关注两个关键组分:SecA,一种由ATP驱动的马达蛋白,负责驱动前体蛋白穿过细胞质膜;以及I型信号肽酶,它负责去除信号肽,使成熟蛋白从膜上释放。我们还鸟瞰了Sec途径中的其他潜在靶点,以及其他Sec依赖性或Sec独立性蛋白质分泌途径,将其作为新型抗生素开发的靶点。本文是名为“细菌中的蛋白质运输与分泌”特刊的一部分。客座编辑:阿纳斯塔西奥斯·埃康诺莫和罗斯·达尔贝。

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