Miles Sydney L, Holt Kathryn E, Mostowy Serge
Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK; Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia.
Trends Microbiol. 2024 Sep;32(9):917-924. doi: 10.1016/j.tim.2024.02.004. Epub 2024 Feb 28.
Shigella is an important human-adapted pathogen which contributes to a large global burden of diarrhoeal disease. Together with the increasing threat of antimicrobial resistance and lack of an effective vaccine, there is great urgency to identify novel therapeutics and preventatives to combat Shigella infection. In this review, we discuss the development of innovative technologies and animal models to study mechanisms underlying Shigella infection of humans. We examine recent literature introducing (i) the organ-on-chip model, and its substantial contribution towards understanding the biomechanics of Shigella infection, (ii) the zebrafish infection model, which has delivered transformative insights into the epidemiological success of clinical isolates and the innate immune response to Shigella, (iii) a pioneering oral mouse model of shigellosis, which has helped to discover new inflammasome biology and protective mechanisms against shigellosis, and (iv) the controlled human infection model, which has been effective in translating basic research into human health impact and assessing suitability of novel vaccine candidates. We consider the recent contributions of each model and discuss where the future of modelling Shigella infection lies.
志贺氏菌是一种重要的适应人类的病原体,它在全球范围内导致了大量的腹泻疾病负担。随着抗菌药物耐药性威胁的增加以及缺乏有效的疫苗,迫切需要确定新的治疗方法和预防措施来对抗志贺氏菌感染。在这篇综述中,我们讨论了用于研究志贺氏菌感染人类潜在机制的创新技术和动物模型的发展。我们审视了近期的文献,内容包括:(i)芯片器官模型及其对理解志贺氏菌感染生物力学的重大贡献;(ii)斑马鱼感染模型,它为临床分离株的流行病学成功以及对志贺氏菌的先天免疫反应提供了变革性见解;(iii)一种开创性的志贺氏菌病口服小鼠模型,它有助于发现新的炎性小体生物学以及针对志贺氏菌病的保护机制;(iv)受控人类感染模型,它有效地将基础研究转化为对人类健康的影响,并评估新型候选疫苗的适用性。我们考虑了每个模型的近期贡献,并讨论了志贺氏菌感染建模的未来方向。