Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, Bethesda, Maryland, USA.
Expert Rev Anti Infect Ther. 2020 Jun;18(6):499-510. doi: 10.1080/14787210.2020.1750951. Epub 2020 Apr 13.
: The emergence of multi- and pan-drug-resistant bacteria represents a global crisis that calls for the development of alternative anti-infective strategies. These comprise anti-virulence approaches, which target pathogenicity without exerting a bacteriostatic or bactericidal effect and are claimed to reduce the development of resistance. Because in many pathogens, quorum-sensing (QS) systems control the expression of virulence factors, interference with QS, or quorum-quenching, is often proposed as a strategy with a broad anti-virulence effect.: We discuss the role and regulatory targets of QS control in selected Gram-positive and Gram-negative bacteria, focusing on those with clinical importance and QS control of virulence. We present the components of QS systems that form possible targets for the development of anti-virulence drugs and discuss recent research on quorum-quenching approaches to control bacterial infection.: While there has been extensive research on QS systems and quorum-quenching approaches, there is a paucity of in-vivo research using adequate animal models to substantiate applicability. In-vivo research on QS blockers needs to be intensified and optimized to use clinically relevant setups, in order to underscore that such drugs can be used effectively to overcome problems associated with the treatment of severe infections by antibiotic-resistant pathogens.
: 多药和泛耐药细菌的出现代表了一场全球性危机,需要开发替代抗感染策略。这些策略包括抗病毒方法,其目的是在不产生抑菌或杀菌作用的情况下靶向致病性,据称可以降低耐药性的发展。因为在许多病原体中,群体感应 (QS) 系统控制着毒力因子的表达,因此干扰 QS 或群体淬灭通常被提议作为一种具有广泛抗病毒作用的策略。: 我们讨论了 QS 控制在选定的革兰氏阳性和革兰氏阴性细菌中的作用和调节靶点,重点关注那些具有临床重要性和 QS 控制毒力的细菌。我们介绍了 QS 系统的组成部分,这些组成部分可能成为抗病毒药物开发的目标,并讨论了最近关于使用群体淬灭方法控制细菌感染的研究。: 虽然已经对 QS 系统和群体淬灭方法进行了广泛的研究,但使用适当的动物模型进行体内研究的情况很少,无法证实其适用性。需要加强和优化 QS 阻断剂的体内研究,以使用临床相关的设置,以强调此类药物可有效用于克服与治疗抗生素耐药病原体引起的严重感染相关的问题。