Krueger Eric, Brown Angela C
Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015 USA.
J Biol Eng. 2019 Feb 19;13:4. doi: 10.1186/s13036-018-0138-z. eCollection 2019.
Over recent years, the development of new antibiotics has not kept pace with the rate at which bacteria develop resistance to these drugs. For this reason, many research groups have begun to design and study alternative therapeutics, including molecules to specifically inhibit the virulence of pathogenic bacteria. Because many of these pathogenic bacteria release protein toxins, which cause or exacerbate disease, inhibition of the activity of bacterial toxins is a promising anti-virulence strategy. In this review, we describe several approaches to inhibit the initial interactions of bacterial toxins with host cell membrane components. The mechanisms by which toxins interact with the host cell membrane components have been well-studied over the years, leading to the identification of therapeutic targets, which have been exploited in the work described here. We review efforts to inhibit binding to protein receptors and essential membrane lipid components, complex assembly, and pore formation. Although none of these molecules have yet been demonstrated in clinical trials, the in vitro and in vivo results presented here demonstrate their promise as novel alternatives and/or complements to traditional antibiotics.
近年来，新型抗生素的研发速度未能跟上细菌对这些药物产生耐药性的速度。因此，许多研究小组已开始设计和研究替代疗法，包括专门抑制病原菌毒力的分子。由于许多病原菌会释放导致或加剧疾病的蛋白质毒素，抑制细菌毒素的活性是一种很有前景的抗毒力策略。在这篇综述中，我们描述了几种抑制细菌毒素与宿主细胞膜成分初始相互作用的方法。多年来，毒素与宿主细胞膜成分相互作用的机制已得到充分研究，从而确定了治疗靶点，本文所述的工作中已对这些靶点加以利用。我们综述了抑制与蛋白质受体和必需膜脂成分结合、复合物组装以及孔形成的相关研究。尽管这些分子尚未在临床试验中得到验证，但本文展示的体外和体内实验结果表明，它们有望成为传统抗生素的新型替代品和/或补充剂。
