Cancer Biology Program, ‡Department of Pathology, §Department of Microbiology and Immunology, and ∥Department of Chemical and Systems Biology, Stanford University School of Medicine , 300 Pasteur Drive, Stanford, California 94305, United States.
Chem Rev. 2017 Mar 8;117(5):4422-4461. doi: 10.1021/acs.chemrev.6b00676. Epub 2017 Feb 24.
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.
抗生素耐药性是一个重大的新兴健康威胁。加剧这一问题的原因包括抗生素的过度处方以及新抗菌药物的研发不足。一种向开发针对细菌病原体毒力因子的非抗生素药物转变的范式，可以开始解决耐药性问题。特别值得关注的是针对细菌 AB 毒素的化合物，这些化合物有可能在不损害健康共生微生物菌群的情况下，预防毒素引起的病理变化。成功开发抗毒素药物可能会减少抗生素的使用，从而减少导致抗生素耐药性突变的选择压力。此外，抗毒素药物不仅在治疗应用方面有很大的前景，而且还可以作为继续研究细菌发病机制的工具。在这篇综述中，我们讨论了越来越多的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的例子。
