Ethanolamine is a valuable nutrient source that impacts Clostridium difficile pathogenesis.

Ethanolamine is a valuable nutrient source that impacts Clostridium difficile pathogenesis.
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DOI:
10.1111/1462-2920.14048
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发表时间:
2018-04
影响因子:
5.1
通讯作者:
McBride SM
McBride SM
中科院分区:
生物学2区
文献类型:
--
作者:
Nawrocki KL;Wetzel D;Jones JB;Woods EC;McBride SM

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艰难梭菌 (Clostridioides) 是一种胃肠道病原体,寄居在哺乳动物的肠道中,可引起严重的腹泻病。尽管艰难梭菌的生长仅限于肠道,但我们对细菌生长重要的特定代谢物和宿主因素的了解是有限的。在其他肠道病原体中,膜衍生的代谢物乙醇胺 (EA) 被用作营养源,并可作为启动毒力因子产生的信号。在本研究中,我们研究了乙醇胺的影响以及预测的乙醇胺基因簇 (CD1907-CD1925) 对艰难梭菌生长的作用。使用定向诱变,我们破坏了 eut 簇内的基因,并评估了它们在乙醇胺利用中的作用,以及 eut 破坏对仓鼠疾病模型感染结果的影响。我们的结果表明,eut 基因簇是艰难梭菌以乙醇胺作为主要营养源生长所必需的。此外,无法利用乙醇胺导致动物模型中毒力更大,发病时间更短。总体而言,这些数据表明乙醇胺是宿主内的重要营养源,并且与其他肠道病原体相比,艰难梭菌对乙醇胺的代谢可以延缓疾病的发作。
Clostridium (Clostridioides) difficile is a gastrointestinal pathogen that colonizes the intestinal tract of mammals and can cause severe diarrheal disease. Although C. difficile growth is confined to the intestinal tract, our understanding of the specific metabolites and host factors that are important for the growth of the bacterium is limited. In other enteric pathogens, the membrane-derived metabolite, ethanolamine (EA), is utilized as a nutrient source and can function as a signal to initiate the production of virulence factors. In this study, we investigated the effects of ethanolamine and the role of the predicted ethanolamine gene cluster (CD1907–CD1925) on C. difficile growth. Using targeted mutagenesis, we disrupted genes within the eut cluster and assessed their roles in ethanolamine utilization, and the impact of eut disruption on the outcome of infection in a hamster model of disease. Our results indicate that the eut gene cluster is required for the growth of C. difficile on ethanolamine as a primary nutrient source. Further, the inability to utilize ethanolamine resulted in greater virulence and a shorter time to morbidity in the animal model. Overall, these data suggest that ethanolamine is an important nutrient source within the host and that, in contrast to other intestinal pathogens, the metabolism of ethanolamine by C. difficile can delay the onset of disease.
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