Investigation of the localization of Filamentous temperature sensitive protein Z (FtsZ) in pathogenic E. coli as a biomarker for antibacterial agents.

抗菌素耐药性问题在世界范围内非常严重，需要采取新的方法来解决这一问题。与人类健康有关的部分问题是，社区和医院环境中存在对小分子抗生素具有高度耐药性的细菌，导致治疗结果延迟、再感染甚至死亡。在本项目中，我们希望在细菌发病机制的背景下开发和探索宿主-病原体相互作用的模型系统，并将其用于研究和发现新型抗菌剂。对于这个模型，我们将使用大肠杆菌O18:K1:H7，结合人大脑微血管内皮细胞系（hCMEC/D3）建立体外新生儿脑膜炎模型。我们的方法将是在这种人类细胞系感染模型中监测杆状大肠杆菌的生长，重点关注作为细菌细胞分裂和生长标记的细胞分裂蛋白FtsZ。我们的目的是研究FtsZ或相关标记物在噬菌体应用后是否会发生变化，以及这些标记物是否可以作为新型抗菌剂的生物标记物。

The problem of antimicrobial resistance is very severe worldwide and new approaches are required to tackle it. Part of the problem in relation to human health is the presence of highly resistant bacteria to small molecule antibiotics in community and hospital settings, leading to delayed treatment outcomes, reinfection or even death. In this project we wish to develop and explore a model system for host-pathogen interaction in the context of bacterial pathogenesis and its utility in the study and discovery on novel antibacterial agents. For this model, we will use E. coli O18:K1:H7, in conjunction with a human cerebral microvascular endothelial cell line (hCMEC/D3) to establish an in-vitro neonatal meningitis model. Our approach will be to monitor the growth of rod-shaped E. coli in this human cell line infection model focussing on the cell division protein FtsZ as a marker for bacterial cell division and growth. We aim to investigate whether the FtsZ or relevant markers go through changes upon bacteriophage application and whether these can be used as biomarkers for novel antimicrobials.