Research in a time of enteroids and organoids: how the human gut model has transformed the study of enteric bacterial pathogens.
Research in a time of enteroids and organoids: how the human gut model has transformed the study of enteric bacterial pathogens.
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DOI：
10.1080/19490976.2020.1795389
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Barry EM
中科院分区：
文献类型：
--
作者：
Ranganathan S;Smith EM;Foulke-Abel JD;Barry EM
肠道细菌病原体在全球范围内造成显着的发病率和死亡率。组织培养和动物模型的研究塑造了我们对这些宿主与病原体相互作用的初步理解。然而，这些模型的内在缺陷限制了它们的应用，特别是在药物筛选和疫苗开发等转化应用中。人肠道肠类和类器官模型克服了现有模型的一些局限性，推进了肠道病原体的研究。在这篇综述中，我们详细介绍了使用人类肠类和类器官来研究侵袭性细菌志贺氏菌、李斯特菌和沙门氏菌，以及非侵袭性细菌致病性大肠杆菌、艰难梭菌和霍乱弧菌的发病机制。我们强调这些研究如何证实先前确定的机制，并且更重要的是揭示新的机制。我们还讨论了模型进展的挑战，包括整合环境条件、先天免疫细胞和固有微生物组的平台工程，以及最近开发的抗菌药物和疫苗的临床前测试的潜力。
Enteric bacterial pathogens cause significant morbidity and mortality globally. Studies in tissue culture and animal models shaped our initial understanding of these host–pathogen interactions. However, intrinsic shortcomings in these models limit their application, especially in translational applications like drug screening and vaccine development. Human intestinal enteroid and organoid models overcome some limitations of existing models and advance the study of enteric pathogens. In this review, we detail the use of human enteroids and organoids to investigate the pathogenesis of invasive bacteria Shigella, Listeria, and Salmonella, and noninvasive bacteria pathogenic Escherichia coli, Clostridium difficile, and Vibrio cholerae. We highlight how these studies confirm previously identified mechanisms and, importantly, reveal novel ones. We also discuss the challenges for model advancement, including platform engineering to integrate environmental conditions, innate immune cells and the resident microbiome, and the potential for pre-clinical testing of recently developed antimicrobial drugs and vaccines.
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DOI：
10.1073/pnas.1811866115
发表时间：
2018-10-02
影响因子：
11.1
作者：
Forbester JL;Lees EA;Goulding D;Forrest S;Yeung A;Speak A;Clare S;Coomber EL;Mukhopadhyay S;Kraiczy J;Schreiber F;Lawley TD;Hancock REW;Uhlig HH;Zilbauer M;Powrie F;Dougan G
通讯作者：
Dougan G
影响因子：
29.4
作者：
Foulke-Abel J;In J;Yin J;Zachos NC;Kovbasnjuk O;Estes MK;de Jonge H;Donowitz M
通讯作者：
Donowitz M
DOI：
10.1016/j.ejpb.2017.07.013
发表时间：
2017-10-01
影响因子：
4.9
作者：
Ahmad, Tauseef;Gogarty, Martina;Brayden, David J.
通讯作者：
Brayden, David J.
影响因子：
11.8
作者：
Dundas, S;Todd, WTA;Hutchinson, SJ
通讯作者：
Hutchinson, SJ
影响因子：
6.4
作者：
Finkbeiner SR;Zeng XL;Utama B;Atmar RL;Shroyer NF;Estes MK
通讯作者：
Estes MK