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微生物可利用肠道上皮细胞死亡诱导的营养释放
2021-08-08 12:22

比利时根特大学生物医学分子生物学系Ravichandran, Kodi S.研究组发现微生物可利用肠道上皮细胞死亡诱导的营养释放。该研究于2021年8月4日发表于国际一流学术期刊《自然》杂志上。

他们提出了一个概念,即包括患者来源的临床分离株在内的几种肠杆菌科细菌具有有效的生长策略,可以利用垂死的肠道上皮细胞释放的可溶性因子。在 caspase-3/7 依赖性细胞凋亡后释放的哺乳动物营养物质促进多种肠杆菌的生长,并使用原代小鼠结肠组织、小鼠和人类细胞系、几种细胞凋亡触发器以及在体内常规和无菌小鼠中观察到。哺乳动物细胞死亡营养素在致病性沙门氏菌中诱导核心转录反应,他们将丙酮酸形式-裂解酶编码 pflB 基因确定为三种情况下细菌定植的关键驱动因素:食源性感染模型、依赖于 TNF 和 A20 的细胞死亡模型和化疗诱导的粘膜炎模型。这些发现为复杂的宿主 - 病原体相互作用引入了一个新层,其中死亡诱导的营养释放作为肠道细菌的燃料来源,对肠胃炎症和细胞毒性化疗治疗产生影响。

据悉,受调节的细胞死亡是生命的一个组成部分,对生物体发育和体内平衡有广泛的影响。受调节的细胞死亡过程中的故障,包括死亡细胞的清除,可以在包括胃肠道在内的各种组织的各种病理中表现出来。细胞死亡和胃肠道病理之间存在一种长期受到关注但难以明确定义的关系,其中包含潜在的微生物成分,但哺乳动物细胞死亡对细菌生长的直接影响尚不清楚。

附:英文原文

Title: Microbes exploit death-induced nutrient release by gut epithelial cells

Author: Anderson, Christopher J., Medina, Christopher B., Barron, Brady J., Karvelyte, Laura, Aaes, Tania Lve, Lambertz, Irina, Perry, Justin S. A., Mehrotra, Parul, Gonalves, Amanda, Lemeire, Kelly, Blancke, Gillian, Andries, Vanessa, Ghazavi, Farzaneh, Martens, Arne, van Loo, Geert, Vereecke, Lars, Vandenabeele, Peter, Ravichandran, Kodi S.

Issue&Volume: 2021-08-04

Abstract: Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis1. Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract2. A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component3,4,5,6, but the direct effect of dying mammalian cells on bacterial growth is unclear. Here we advance a concept that several Enterobacteriaceae, including patient-derived clinical isolates, have an efficient growth strategy to exploit soluble factors that are released from dying gut epithelial cells. Mammalian nutrients released after caspase-3/7-dependent apoptosis boosts the growth of multiple Enterobacteriaceae and is observed using primary mouse colonic tissue, mouse and human cell lines, several apoptotic triggers, and in conventional as well as germ-free mice in vivo. The mammalian cell death nutrients induce a core transcriptional response in pathogenic Salmonella, and we identify the pyruvate formate-lyase-encoding pflB gene as a key driver of bacterial colonization in three contexts: a foodborne infection model, a TNF- and A20-dependent cell death model, and a chemotherapy-induced mucositis model. These findings introduce a new layer to the complex host–pathogen interaction, in which death-induced nutrient release acts as a source of fuel for intestinal bacteria, with implications for gut inflammation and cytotoxic chemotherapy treatment.

DOI: 10.1038/s41586-021-03785-9

Source: https://www.nature.com/articles/s41586-021-03785-9

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
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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