Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland 20814, USA.
Nat Rev Drug Discov. 2017 Jul;16(7):457-471. doi: 10.1038/nrd.2017.23. Epub 2017 Mar 24.
The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways - the target of traditional antibiotics - intact. Either as stand-alone medications or together with antibiotics, these drugs are intended to treat bacterial infections in a largely pathogen-specific manner. Notably, development of antivirulence drugs requires an in-depth understanding of the roles that diverse virulence factors have in disease processes. In this Review, we outline the theory behind antivirulence strategies and provide examples of bacterial features that can be targeted by antivirulence approaches. Furthermore, we discuss the recent successes and failures of this paradigm, and new developments that are in the pipeline.
细菌病原体对抗生素耐药性的快速进化和传播速度超过了新抗生素的研发速度，但抗毒剂提供了一种替代方法。这些药物可以通过消除使人类患病的毒力因子来规避抗生素耐药性，同时保持细菌生长途径不变——这是传统抗生素的作用靶点。这些药物可以作为单一药物或与抗生素一起使用，旨在以主要针对病原体的方式治疗细菌感染。值得注意的是，开发抗毒药物需要深入了解各种毒力因子在疾病过程中所起的作用。在这篇综述中，我们概述了抗毒策略的理论，并提供了可以通过抗毒方法靶向的细菌特征的实例。此外，我们还讨论了这一范例的最新成功和失败案例，以及正在研发中的新进展。
