Huerta-Uribe Alejandro, Roe Andrew J
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, U.K.
Emerg Top Life Sci. 2017 Apr 21;1(1):31-39. doi: 10.1042/ETLS20160013.
The rapid emergence of antibiotic-resistant bacterial strains has prompted efforts to find new and more efficacious treatment strategies. Targeting virulence factors produced by pathogenic bacteria has gained particular attention in the last few years. One of the inherent advantages of this approach is that it provides less selective pressure for the development of resistance mechanisms. In addition, antivirulence drugs could potentially be the answer for diseases in which the use of conventional antibiotics is counterproductive. That is the case for bacterial toxin-mediated diseases, in which the severity of the symptoms is a consequence of the exotoxins produced by the pathogen. Examples of these are haemolytic-uraemic syndrome produced by Shiga toxins, the profuse and dangerous dehydration caused by Cholera toxin or the life-threatening colitis occasioned by clostridial toxins. This review focuses on the recent advances on the development of small molecules with antitoxin activity against Enterohaemorrhagic Escherichia coli, Vibrio cholerae and Clostridium difficile given their epidemiological importance. The present work includes studies of small molecules with antitoxin properties that act directly on the toxin (direct inhibitors) or that act by preventing expression of the toxin (indirect inhibitors).
抗生素耐药性细菌菌株的迅速出现促使人们努力寻找新的、更有效的治疗策略。在过去几年中，针对病原菌产生的毒力因子的研究受到了特别关注。这种方法的一个固有优势是，它为耐药机制的发展提供了较小的选择压力。此外，抗毒力药物可能是解决使用传统抗生素适得其反的疾病的答案。细菌毒素介导的疾病就是这种情况，其中症状的严重程度是病原体产生的外毒素的结果。这些疾病的例子包括志贺毒素引起的溶血尿毒综合征、霍乱毒素导致的大量危险脱水或梭菌毒素引发的危及生命的结肠炎。鉴于它们在流行病学上的重要性，本综述重点关注具有抗毒素活性的小分子针对肠出血性大肠杆菌、霍乱弧菌和艰难梭菌的开发进展。目前的工作包括对抗毒素特性的小分子的研究，这些小分子直接作用于毒素（直接抑制剂）或通过阻止毒素的表达起作用（间接抑制剂）。
