Critical Role of Zinc in a New Murine Model of Enterotoxigenic Escherichia coli Diarrhea.
Critical Role of Zinc in a New Murine Model of Enterotoxigenic Escherichia coli Diarrhea.
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DOI：
10.1128/iai.00183-18
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发表时间：
2018-07
影响因子：
3.1
通讯作者：
Guerrant RL
中科院分区：
文献类型：
--
作者：
Bolick DT;Medeiros PHQS;Ledwaba SE;Lima AAM;Nataro JP;Barry EM;Guerrant RL
产肠毒素大肠杆菌（ETEC）是发展中地区儿童旅行者腹泻以及地方性腹泻和发育迟缓的主要原因。然而，迫切需要一个小型哺乳动物模型来更好地理解和评估机制、疫苗和干预措施。我们报道了一个ETEC腹泻、体重减轻和肠病的小鼠模型，并研究了锌在结果中的作用。在抗生素破坏正常菌群后，将产热不稳定毒素（LT）和热稳定毒素（ST）的ETEC菌株给予断奶C57BL/6小鼠，造成生长障碍、水样腹泻、大量排便和轻度至中度肠道炎症，后者在缺锌时更为严重。锌处理促进了锌缺乏感染小鼠的生长，锌的亚抑制水平降低了ETEC毒力基因cfa1、cexE、sta2和degP的表达，但对eltA没有影响。锌的补充增加了野生型ETEC的脱毛量和回肠负荷，但降低了LT敲除型ETEC的脱毛量和组织负荷。通过粪便髓过氧化物酶（MPO）评估，LTKO etec感染小鼠的疾病发作延迟，炎症也较少。这些发现提供了一种新的小鼠ETEC感染模型，可以帮助阐明生长、腹泻和炎症反应的机制，以及潜在的疫苗和干预措施。
Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveler's diarrhea as well as of endemic diarrhea and stunting in children in developing areas. However, a small-mammal model has been badly needed to better understand and assess mechanisms, vaccines, and interventions. We report a murine model of ETEC diarrhea, weight loss, and enteropathy and investigate the role of zinc in the outcomes. ETEC strains producing heat-labile toxins (LT) and heat-stable toxins (ST) that were given to weaned C57BL/6 mice after antibiotic disruption of normal microbiota caused growth impairment, watery diarrhea, heavy stool shedding, and mild to moderate intestinal inflammation, the latter being worse with zinc deficiency. Zinc treatment promoted growth in zinc-deficient infected mice, and subinhibitory levels of zinc reduced expression of ETEC virulence genes cfa1, cexE, sta2, and degP but not of eltA in vitro. Zinc supplementation increased shedding and the ileal burden of wild-type (WT) ETEC but decreased shedding and the tissue burden of LT knockout (LTKO) ETEC. LTKO ETEC-infected mice had delayed disease onset and also had less inflammation by fecal myeloperoxidase (MPO) assessment. These findings provide a new murine model of ETEC infection that can help elucidate mechanisms of growth, diarrhea, and inflammatory responses as well as potential vaccines and interventions.