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抗志贺毒素的治疗性抗体:趋势与展望。

Therapeutic Antibodies Against Shiga Toxins: Trends and Perspectives.

机构信息

Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.

Laboratorio de Fisiopatogenia, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

出版信息

Front Cell Infect Microbiol. 2022 Feb 10;12:825856. doi: 10.3389/fcimb.2022.825856. eCollection 2022.

Abstract

Shiga toxins (Stx) are AB-type toxins, composed of five B subunits which bind to Gb host cell receptors and an active A subunit, whose action on the ribosome leads to protein synthesis suppression. The two Stx types (Stx1 and Stx2) and their subtypes can be produced by Shiga toxin-producing strains and some spp. These bacteria colonize the colon and induce diarrhea that may progress to hemorrhagic colitis and in the most severe cases, to hemolytic uremic syndrome, which could lead to death. Since the use of antibiotics in these infections is a topic of great controversy, the treatment remains supportive and there are no specific therapies to ameliorate the course. Therefore, there is an open window for Stx neutralization employing antibodies, which are versatile molecules. Indeed, polyclonal, monoclonal, and recombinant antibodies have been raised and tested and assays, showing differences in their neutralizing ability against deleterious effects of Stx. These molecules are in different phases of development for which we decide to present herein an updated report of these antibody molecules, their source, advantages, and disadvantages of the promising ones, as well as the challenges faced until reaching their applicability.

摘要

志贺毒素(Stx)是一种 AB 型毒素,由五个 B 亚基组成,这些 B 亚基与 Gb 宿主细胞受体结合,而活性 A 亚基在核糖体上起作用,导致蛋白质合成抑制。两种志贺毒素类型(Stx1 和 Stx2)及其亚型可由产志贺毒素菌株和一些 spp 产生。这些细菌定植于结肠并诱导腹泻,腹泻可能进展为出血性结肠炎,在最严重的情况下,进展为溶血性尿毒综合征,可能导致死亡。由于在这些感染中使用抗生素是一个极具争议的话题,因此治疗仍然是支持性的,没有专门的疗法可以改善病程。因此,使用抗体中和 Stx 有一个开放的窗口,抗体是多功能分子。事实上,已经制备和测试了多克隆、单克隆和重组抗体,以及 测定,显示它们对 Stx 有害影响的中和能力存在差异。这些分子处于不同的开发阶段,我们决定在此介绍这些抗体分子的最新报告,包括它们的来源、优势和劣势,以及在达到适用性之前面临的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ee2/8866733/9c684c4d48fc/fcimb-12-825856-g001.jpg

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