In vitro models of Neisseria gonorrhoeae infection to study resistance acquisition and inform the selection of novel treatment strategies.

耐抗生素淋病奈瑟菌是一种发展中的严重威胁。淋病奈瑟菌目前被列入世卫组织迫切需要新抗生素的病原体重点清单。开发新药以应对耐多药和广泛耐药威胁的一个主要障碍是缺乏健全和可预测的模型。本项目旨在建立更具代表性的淋病奈瑟菌细胞内和细胞外感染模型。动态活细胞共聚焦成像和流式细胞术方法将用于表征适当的人类细胞系的感染动力学。生成的定量数据将用于根据PK/PD建模将给药方案转化为人类。开发新的和强大的药物开发模型来调查耐多药和广泛耐药的威胁，对于确定药物的优先次序、选择药物组合和选择治疗方案至关重要。

Antibiotic resistant Neisseria gonorrhoeae is a developing and serious threat. N. gonorrhoeae is currently listed on the WHO priority list of pathogens for which new antibiotics are urgently needed. A major obstacle to the development of new drugs to address the threat of MDR and XDR is the absence of robust and predictable models. This project will aim to develop more representative intracellular and extracellular models of N. gonorrhoeae infection. Kinetic live-cell confocal imaging and flow cytometric methods will be used to characterise infection dynamics in appropriate human cell lines. The quantitative data generated will be used to translate dosing regimens to humans following PK/PD modelling. Developing novel and robust drug development models to investigate the threat of MDR and XDR is essential for the prioritisation of drugs, the selection of drug combinations and regimen selection.