Institute of Infectiology, Center for Molecular Biology of Inflammation (ZMBE), Westfälische Wilhelms-Universität Münster, Von-Esmarch-Strasse 56, 48149 Münster, Germany.
Trends Biotechnol. 2017 Feb;35(2):109-120. doi: 10.1016/j.tibtech.2016.08.002. Epub 2016 Sep 1.
Bacterial pathogens have developed intriguing virulence mechanisms, including several sophisticated nanomachines, for injecting effector proteins to manipulate host immune signaling pathways for their own benefit. Therefore, bacterial genomes harbor a wealth of information about how to manipulate the defense systems of the host. Current understanding addresses virulence mechanisms mostly as targets for antimicrobials. We propose a change of paradigm by exploiting bacterial effectors not as targets but as tools for the directed manipulation of host signaling - for the benefit of the host. Recently, effector proteins have been identified that autonomously translocate into host cells, representing a novel class of cell-penetrating peptides (CPPs) or effectors (CPEs). Moreover, autonomous cell penetration overcomes a major hurdle in pharmacology by transducing specific therapeutic agents to intracellular targets.
细菌病原体已经开发出有趣的毒力机制，包括几种复杂的纳米机器，用于注射效应蛋白来操纵宿主的免疫信号通路，以谋取自身利益。因此，细菌基因组蕴藏着大量关于如何操纵宿主防御系统的信息。目前的研究主要将毒力机制视为抗菌药物的靶点。我们建议改变范式，利用细菌效应物不是作为靶点，而是作为宿主信号定向操纵的工具——为了宿主的利益。最近，已经鉴定出自主易位进入宿主细胞的效应蛋白，这代表了一类新型的细胞穿透肽（CPP）或效应物（CPE）。此外，自主细胞穿透克服了药理学中的一个主要障碍，即将特定的治疗剂转导到细胞内靶标。
