Role of Ethanolamine Utilization Genes in Host Colonization during Urinary Tract Infection
Role of Ethanolamine Utilization Genes in Host Colonization during Urinary Tract Infection
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乙醇胺利用基因在尿路感染宿主定植中的作用
DOI：
10.1128/iai.00542-17
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发表时间：
2017-12
影响因子：
3.1
通讯作者：
A. Sintsova;Sara N Smith;S. Subashchandrabose;H. Mobley
中科院分区：
文献类型：
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作者：
A. Sintsova;Sara N Smith;S. Subashchandrabose;H. Mobley
摘要泌尿道感染（UTI）是人类第二大常见感染，是全球卫生工作的重点。近一半的女性会经历有症状的UTI，尿路致病性大肠杆菌（UPEC）是感染的主要病原体。尽管对UPEC毒力决定因素进行了广泛的研究，但宿主特异性代谢的重要性仍然未得到充分研究。我们在这里报告，UPEC上调乙醇胺利用基因的表达，在简单的UTI在人类。我们进一步表明，UPEC乙醇胺代谢是上行性UTI小鼠模型中有效膀胱定植所需的，并且是免疫功能低下的UTI小鼠模型中膀胱定植所必需的。我们证明，虽然乙醇胺代谢突变体没有表现出增加的敏感性，中性粒细胞的抗菌反应，这种代谢途径是重要的生存先天免疫系统在UTI。这项研究揭示了宿主中UPEC代谢的一个新方面，并为细菌代谢与宿主免疫反应之间未被充分认识的联系提供了证据。
ABSTRACT Urinary tract infection (UTI) is the second most common infection in humans, making it a global health priority. Nearly half of all women will experience a symptomatic UTI, with uropathogenic Escherichia coli (UPEC) being the major causative agent of the infection. Although there has been extensive research on UPEC virulence determinants, the importance of host-specific metabolism remains understudied. We report here that UPEC upregulates the expression of ethanolamine utilization genes during uncomplicated UTIs in humans. We further show that UPEC ethanolamine metabolism is required for effective bladder colonization in the mouse model of ascending UTI and is dispensable for bladder colonization in an immunocompromised mouse model of UTI. We demonstrate that although ethanolamine metabolism mutants do not show increased susceptibility to antimicrobial responses of neutrophils, this metabolic pathway is important for surviving the innate immune system during UTI. This study reveals a novel aspect of UPEC metabolism in the host and provides evidence for an underappreciated link between bacterial metabolism and the host immune response.