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艰难梭菌可利用疾病过程中产生的宿主代谢产物
2021-04-30 15:23

美国斯坦福大学医学院Justin L. Sonnenburg课题组经过不懈努力而取得。他们发现艰难梭菌利用毒素介导的疾病过程中产生的宿主代谢产物。相关论文于2021年4月28日发表于国际顶尖学术期刊《自然》杂志上。

为了了解艰难梭菌的代谢如何适应其毒素诱导的炎症条件,他们使用RNA测序在小鼠模型中定义了野生型艰难梭菌和缺乏毒素的同基因突变体的代谢状态。通过结合细菌和小鼠的遗传学,他们证明艰难梭菌使用源自饮食和宿主的山梨糖醇。宿主来源的山梨糖醇是由醛糖还原酶产生的,醛糖还原酶由多种免疫细胞表达,并在炎症过程中被上调,包括艰难梭菌诱导的毒素介导的疾病。这项工作强调了艰难梭菌可以利用宿主来源的营养物的机制,该营养物是在毒素诱导的疾病期间通过以前未与感染相关的酶产生的。

据悉,与肠道菌群其他成员相比,几种肠道病原体可以通过诱导宿主病理学和炎症而获得特定的代谢优势。病原体艰难梭菌是由毒素介导的结肠炎的原因,每年在美国引起45万例感染和15,000例死亡。然而,艰难梭菌从这种病理学中受益的分子机制仍然不清楚。

附:英文原文

Title: C. difficile exploits a host metabolite produced during toxin-mediated disease

Author: Kali M. Pruss, Justin L. Sonnenburg

Issue&Volume: 2021-04-28

Abstract: Several enteric pathogens can gain specific metabolic advantages over other members of the microbiota by inducing host pathology and inflammation. The pathogen Clostridium difficile is responsible for a toxin-mediated colitis that causes 450,000 infections and 15,000 deaths in the United States each year1; however, the molecular mechanisms by which C. difficile benefits from this pathology remain unclear. To understand how the metabolism of C. difficile adapts to the inflammatory conditions that its toxins induce, here we use RNA sequencing to define, in a mouse model, the metabolic states of wild-type C. difficile and of an isogenic mutant that lacks toxins. By combining bacterial and mouse genetics, we demonstrate that C. difficile uses sorbitol derived from both diet and host. Host-derived sorbitol is produced by the enzyme aldose reductase, which is expressed by diverse immune cells and is upregulated during inflammation—including during toxin-mediated disease induced by C. difficile. This work highlights a mechanism by which C. difficile can use a host-derived nutrient that is generated during toxin-induced disease by an enzyme that has not previously been associated with infection.

DOI: 10.1038/s41586-021-03502-6

Source: https://www.nature.com/articles/s41586-021-03502-6

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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