Microbiotix, Inc., Worcester, MA, USA.
Microbiotix, Inc., Worcester, MA, USA.
Drug Discov Today. 2021 Sep;26(9):2173-2181. doi: 10.1016/j.drudis.2021.03.031. Epub 2021 Apr 9.
The increasing prevalence of multidrug-resistant (MDR) bacterial infections has created a crucial need for new therapeutics that avoid or minimize existing resistance mechanisms. In this review, we describe the development of novel classes of small-molecule adjunctive agents targeting either a bacterial virulence factor, the Pseudomonas aeruginosa type III secretion system (T3SS), or an intrinsic resistance factor, resistance-nodulation-cell division superfamily (RND) efflux pumps of the Enterobacteriaceae. These agents are designed to be administered with antibacterials to improve their efficacy. T3SS inhibition rescues host innate immune system cells from injection with bacterial toxins, whereas RND efflux pump inhibition increases antibiotic susceptibility, in both cases improving the efficacy of the combined antibacterial.
多药耐药（MDR）细菌感染的患病率不断上升，这就迫切需要开发新的治疗方法，以避免或最小化现有耐药机制。在这篇综述中，我们描述了新型小分子辅助药物的开发，这些药物针对细菌毒力因子（铜绿假单胞菌 III 型分泌系统（T3SS））或固有耐药因子（肠杆菌科的耐药-结节-分裂超家族（RND）外排泵）。这些药物旨在与抗菌药物联合使用以提高疗效。T3SS 抑制可使宿主先天免疫系统细胞免受细菌毒素的侵害，而 RND 外排泵抑制可增加抗生素的敏感性，在这两种情况下都可提高联合抗菌药物的疗效。
