A novel mouse model of Campylobacter jejuni enteropathy and diarrhea.
A novel mouse model of Campylobacter jejuni enteropathy and diarrhea.
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DOI：
10.1371/journal.ppat.1007083
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发表时间：
2018-03
期刊：
影响因子：
6.7
通讯作者：
Guerrant RL
中科院分区：
文献类型：
--
作者：
Giallourou N;Medlock GL;Bolick DT;Medeiros PH;Ledwaba SE;Kolling GL;Tung K;Guerry P;Swann JR;Guerrant RL
弯曲杆菌感染是腹泻和“环境性肠病”（EE）以及全球生长障碍的主要细菌原因之一。然而，缺乏一个便宜的小动物模型的肠道疾病与弯曲杆菌一直是一个主要的限制，了解其发病机制，干预措施或疫苗的发展。我们描述了一种稳健的标准小鼠模型，该模型可以表现出可再现的血性腹泻或生长失败，这取决于锌或蛋白质缺乏的饮食以及感染前正常微生物群的抗生素改变。锌缺乏和抗生素的使用通过缩小这些小鼠清除病原体的代谢灵活性以及通过促进肠道和全身炎症来为弯曲杆菌感染创造一个利基。该模型中的几种生物标志物和肠道病理学也模拟了人类疾病中所见的生物标志物和肠道病理学。该模型提供了一种新的工具来测试有关疾病发病机制以及目前正在进行的疫苗开发的特定假设。空肠弯曲菌已被确定为肠病和腹泻的主要原因之一。在发展中国家，这些反复的肠道感染往往导致生长缺陷和认知障碍。缺乏弯曲杆菌感染的小动物模型。这是理解弯曲杆菌感染的发病机制以导致治疗性治疗和疫苗的主要障碍。我们已经开发了一种高度可重复的弯曲杆菌感染小鼠模型，其临床结果与营养不良儿童的临床结果相匹配。我们希望这些对弯曲杆菌易感性的见解将导致针对这一主要原因的治疗方法的发展。
Campylobacter infections are among the leading bacterial causes of diarrhea and of ‘environmental enteropathy’ (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche for Campylobacter infection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to test specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress. Campylobacter jejuni has been identified as one of the leading causes of enteropathy and diarrhea. In developing countries, these repeated enteric infections often result in growth deficits and cognitive impairment. There is a lack of small animal models of Campylobacter infection. This is a major hurdle in understanding the pathogenesis of Campylobacter infection in order to lead to therapeutic treatments and vaccines. We have developed a highly reproducible mouse model of Campylobacter infection that has clinical outcomes that match those of malnourished children. We hope that these insights into Campylobacter susceptibility will lead to the development of treatments against this major cause of diarrheal illness.
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影响因子：
4.2
作者：
Iizumi T;Taniguchi T;Yamazaki W;Vilmen G;Alekseyenko AV;Gao Z;Perez Perez GI;Blaser MJ
通讯作者：
Blaser MJ
影响因子：
3.7
作者：
Guerrant RL;Leite AM;Pinkerton R;Medeiros PH;Cavalcante PA;DeBoer M;Kosek M;Duggan C;Gewirtz A;Kagan JC;Gauthier AE;Swann J;Mayneris-Perxachs J;Bolick DT;Maier EA;Guedes MM;Moore SR;Petri WA;Havt A;Lima IF;Prata MM;Michaleckyj JC;Scharf RJ;Sturgeon C;Fasano A;Lima AA
通讯作者：
Lima AA
影响因子：
4.8
作者：
Brand, IA;Kleineke, J
通讯作者：
Kleineke, J
DOI：
10.1093/cid/ciw542
发表时间：
2016-11-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Amour C;Gratz J;Mduma E;Svensen E;Rogawski ET;McGrath M;Seidman JC;McCormick BJ;Shrestha S;Samie A;Mahfuz M;Qureshi S;Hotwani A;Babji S;Trigoso DR;Lima AA;Bodhidatta L;Bessong P;Ahmed T;Shakoor S;Kang G;Kosek M;Guerrant RL;Lang D;Gottlieb M;Houpt ER;Platts-Mills JA;Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) Network Investigators
通讯作者：
Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) Network Investigators
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP