Division of Pharmacology & Toxicology, College of Pharmacy and Institute for Cellular & Molecular Biology, The University of Texas at Austin, Austin, TX, 78712, USA.
J Mol Med (Berl). 2013 Oct;91(10):1131-41. doi: 10.1007/s00109-013-1048-7. Epub 2013 May 12.
Bacterial AB5 toxins are a clinically relevant class of exotoxins that include several well-known members such as Shiga, cholera, and pertussis toxins. Infections with toxin-producing bacteria cause devastating human diseases that affect millions of individuals each year and have no definitive medical treatment. The molecular targets of AB5 toxins reside in the cytosol of infected cells, and the toxins reach the cytosol by trafficking through the retrograde membrane transport pathway that avoids degradative late endosomes and lysosomes. Focusing on Shiga toxin as the archetype member, we review recent advances in understanding the molecular mechanisms involved in the retrograde trafficking of AB5 toxins and highlight how these basic science advances are leading to the development of a promising new therapeutic approach based on inhibiting toxin transport.
细菌 AB5 毒素是一类具有临床相关性的外毒素，包括几种著名的成员，如志贺毒素、霍乱毒素和百日咳毒素。产毒细菌感染会导致严重的人类疾病，每年影响数百万人，目前尚无明确的医学治疗方法。AB5 毒素的分子靶标位于感染细胞的细胞质中，毒素通过逆行膜运输途径到达细胞质，该途径可避免晚期内体和溶酶体的降解。以志贺毒素为原型成员，我们综述了近年来对 AB5 毒素逆行运输所涉及的分子机制的理解进展，并强调了这些基础科学进展如何为基于抑制毒素运输的有前景的新治疗方法的发展提供了依据。
