Antibiotic resistance is a significant emerging health threat. Exacerbating this problem is the overprescription of antibiotics as well as a lack of development of new antibacterial agents. A paradigm shift toward the development of nonantibiotic agents that target the virulence factors of bacterial pathogens is one way to begin to address the issue of resistance. Of particular interest are compounds targeting bacterial AB toxins that have the potential to protect against toxin-induced pathology without harming healthy commensal microbial flora. Development of successful antitoxin agents would likely decrease the use of antibiotics, thereby reducing selective pressure that leads to antibiotic resistance mutations. In addition, antitoxin agents are not only promising for therapeutic applications, but also can be used as tools for the continued study of bacterial pathogenesis. In this review, we discuss the growing number of examples of chemical entities designed to target exotoxin virulence factors from important human bacterial pathogens.

中文翻译：

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针对细菌致病力的化学策略

抗生素耐药性是严重的新兴健康威胁。抗生素的处方过多以及缺乏新的抗菌剂的开发加剧了这一问题。朝着以细菌病原体的致病因子为目标的非抗生素制剂发展的范式转变是开始解决耐药性问题的一种方法。特别感兴趣的是靶向细菌AB毒素的化合物，该化合物具有保护免受毒素诱导的病理变化而不会损害健康的共生微生物菌群的潜力。成功开发抗毒素剂可能会减少抗生素的使用，从而降低导致抗生素耐药性突变的选择性压力。此外，抗毒素剂不仅有望用于治疗应用，但也可以作为细菌致病性研究的工具。在这篇综述中，我们讨论了旨在针对重要人类细菌病原体的外毒素毒力因子的化学实体实例的数量不断增加的情况。