Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
EMBO Mol Med. 2009 Jul;1(4):201-10. doi: 10.1002/emmm.200900032.
The global rise of anti-microbial resistance, combined with the rapid rate of microbial evolution, and the slower development of novel antibiotics, underscores the urgent need for innovative therapeutics. We are facing a post-antibiotic era with a decreased armamentarium to combat infectious diseases. Development of novel drugs will rely on basic research aimed to increase our understanding of bacterial pathogenesis and the inter-cellular chemical signalling among bacterial cells. Such basic science, when combined with contemporary drug discovery technologies, may be translated into therapeutic applications to combat bacterial infections. In this review, we discuss many strategies aimed to interfere with bacterial cell-to-cell signalling via the quorum-sensing (QS) pathway to inhibit bacterial virulence and/or the development of microbial communities (known as biofilms), which are refractory to antibiotic treatment. QS antagonists should be viewed as blockers of pathogenicity rather than as anti-microbials and because QS is not involved in bacterial growth, inhibition of QS should not yield a strong selective pressure for development of resistance. QS inhibitors (QSIs) hold great expectations and we look forward to their application in fighting bacterial infections.
全球范围内抗微生物药物耐药性的上升,加上微生物快速进化的速度,以及新型抗生素开发速度的减缓,凸显了创新治疗方法的迫切需求。我们正面临着一个后抗生素时代,用于对抗传染病的武器库已经减少。新型药物的开发将依赖于旨在提高我们对细菌发病机制和细菌细胞间化学信号传递理解的基础研究。这种基础科学,结合当代药物发现技术,可能转化为治疗细菌感染的应用。在这篇综述中,我们讨论了许多旨在通过群体感应(QS)途径干扰细菌细胞间信号传递的策略,以抑制细菌毒力和/或微生物群落(称为生物膜)的发展,这些生物膜对抗生素治疗有抵抗力。QS 拮抗剂应被视为致病性抑制剂,而不是抗菌剂,因为 QS 不参与细菌生长,抑制 QS 不应产生对耐药性发展的强烈选择压力。QS 抑制剂 (QSIs) 寄予厚望,我们期待它们在对抗细菌感染方面的应用。