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，需要新的方法来解决它。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抗药性的细菌，导致治疗结果延迟、再次感染甚至死亡。在本项目中，我们希望开发和探索细菌发病机制中宿主-病原体相互作用的模型系统，并将其应用于新型抗菌药物的研究和发现。对于这个模型，我们将使用E.ColiO18：K1：H7，结合人脑微血管内皮细胞系(hCMEC/D3)来建立体外新生儿脑膜炎模型。我们的方法将是监测杆状大肠杆菌在这个人类细胞系感染模型中的生长，重点是细胞分裂蛋白FtsZ作为细菌细胞分裂和生长的标志。我们的目标是调查FtsZ或相关标记物在噬菌体应用时是否会发生变化，以及这些标记物是否可以作为新型抗菌药的生物标记物。

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.