Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Trends Pharmacol Sci. 2016 Sep;37(9):734-749. doi: 10.1016/j.tips.2016.05.011. Epub 2016 Jun 22.
The injectisome type three secretion system (T3SS) is a major virulence factor in Pseudomonas aeruginosa. This bacterium is responsible for severe infections in immunosuppressed or cystic fibrosis patients and has become resistant to many antibiotics. Inhibitors of T3SS may therefore constitute an innovative therapeutic target. After a brief description of the T3SS and its regulation, this review presents strategies to inhibit T3SS-mediated toxicity and describes the main families of existing inhibitors. Over the past few years, 12 classes of small-molecule inhibitors and two types of antibody have been discovered and evaluated in vitro for their capacity to inhibit T3SS expression or function, and to protect host cells from T3SS-mediated cytotoxicity. While only one small molecule has been tested in vivo, a bifunctional antibody targeting both the translocation apparatus of the T3SS and a surface polysaccharide is currently in Phase II clinical trials.
III 型分泌系统（T3SS）是铜绿假单胞菌的主要毒力因子。这种细菌会导致免疫抑制或囊性纤维化患者的严重感染，并且对许多抗生素产生了耐药性。因此，T3SS 的抑制剂可能成为一种创新的治疗靶点。在简要描述 T3SS 及其调控之后，本综述介绍了抑制 T3SS 介导的毒性的策略，并描述了现有的主要抑制剂家族。在过去几年中，已经发现了 12 类小分子抑制剂和两种类型的抗体，并在体外评估了它们抑制 T3SS 表达或功能以及保护宿主细胞免受 T3SS 介导的细胞毒性的能力。虽然只有一种小分子在体内进行了测试，但一种针对 T3SS 转位装置和表面多糖的双功能抗体目前正在进行 II 期临床试验。
