Siderophore biosynthesis coordinately modulated the virulence-associated interactive metabolome of uropathogenic Escherichia coli and human urine.
Siderophore biosynthesis coordinately modulated the virulence-associated interactive metabolome of uropathogenic Escherichia coli and human urine.
复制标题
铁载体生物合成协调调节尿路致病性大肠杆菌和人尿液的毒力相关的相互作用代谢组
DOI：
10.1038/srep24099
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发表时间：
2016-04-14
影响因子：
4.6
通讯作者：
Lv H
中科院分区：
文献类型：
--
作者：
Su Q;Guan T;Lv H
尿路感染（UTI）期间，女性膀胱中的尿路致病性大肠杆菌（UPEC）生长引起大量化学交换，称为“相互作用代谢组”，其主要占UPEC和人尿液之间的代谢成本（利用代谢组）和代谢捐赠（排泄代谢组）。在这里，我们试图确定UPEC和人类尿液之间的个性化相互作用代谢组。我们能够通过采用代谢组学和遗传学的组合来区分UPEC和非UPEC。我们的研究结果表明，UPEC和人尿液之间的相互作用代谢组显着不同的非UPEC和人尿液之间，和UPEC引发更强的扰动，在人尿液中的相互作用代谢组。此外，铁载体的生物合成协调调制的个性化的相互作用的代谢组，我们发现这是一个关键组成部分的UPEC的毒力。个体化的毒性相关的相互作用代谢组包含31种不同的代谢物和17种中心代谢途径，这些代谢途径被注释为宿主这些不同的代谢物，包括能量代谢、氨基酸代谢和肠道微生物代谢。这些途径的活动的变化机械地查明了铁载体生物合成的毒性能力。总之，我们的研究结果为UPEC毒力提供了新的见解，我们提出铁载体是进一步发现治疗UPEC诱导的UTI药物的潜在靶点。
Uropathogenic Escherichia coli (UPEC) growth in women’s bladders during urinary tract infection (UTI) incurs substantial chemical exchange, termed the “interactive metabolome”, which primarily accounts for the metabolic costs (utilized metabolome) and metabolic donations (excreted metabolome) between UPEC and human urine. Here, we attempted to identify the individualized interactive metabolome between UPEC and human urine. We were able to distinguish UPEC from non-UPEC by employing a combination of metabolomics and genetics. Our results revealed that the interactive metabolome between UPEC and human urine was markedly different from that between non-UPEC and human urine, and that UPEC triggered much stronger perturbations in the interactive metabolome in human urine. Furthermore, siderophore biosynthesis coordinately modulated the individualized interactive metabolome, which we found to be a critical component of UPEC virulence. The individualized virulence-associated interactive metabolome contained 31 different metabolites and 17 central metabolic pathways that were annotated to host these different metabolites, including energetic metabolism, amino acid metabolism, and gut microbe metabolism. Changes in the activities of these pathways mechanistically pinpointed the virulent capability of siderophore biosynthesis. Together, our findings provide novel insights into UPEC virulence, and we propose that siderophores are potential targets for further discovery of drugs to treat UPEC-induced UTI.