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剖析羟基丙醛(HPA)体系:一种针对人体病原体的有效抗菌剂。

Unraveling the hydroxypropionaldehyde (HPA) system: an active antimicrobial agent against human pathogens.

机构信息

Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, 8092 ETH Zurich, Switzerland.

出版信息

J Agric Food Chem. 2010 Oct 13;58(19):10315-22. doi: 10.1021/jf1010897.

DOI:10.1021/jf1010897
PMID:20845960
Abstract

The hydroxypropionaldehyde (HPA) system is a natural defense system synthesized by the probiotic bacterium Lactobacillus reuteri. To elucidate which of the molecules composing the HPA system (3-hydroxypropionaldehyde (3-HPA), reuterin (HPA dimer), and HPA hydrate) is responsible for the potent antimicrobial activity in biological systems, a combination of biochemical, genetic, and proteomic assays was used. The HPA system reacts with sulfhydryl-containing compounds such as cysteine and reduced glutathione (GSH) in solution. In situ, GSH knock-out Escherichia coli is significantly more susceptible to HPA-mediated cell death than E. coli wild type; GSH supplementation protects either bacteria from HPA attack. Proteomic analysis of HPA-treated bacteria ( Haemophilus influenzae ) revealed induction of redox- and heat shock-related proteins. A new antimicrobial mechanism of HPA is proposed, whereby the activity of HPA leads to depletion of free SH- groups in GSH and proteins through the action of 3-hydroxypropionaldehyde, causing an imbalance of the cellular redox status, ultimately resulting in cell death.

摘要

羟基丙醛(HPA)系统是由益生菌乳杆菌合成的一种天然防御系统。为了阐明 HPA 系统(3-羟基丙醛(3-HPA)、雷替丁(HPA 二聚体)和 HPA 水合物)中的哪种分子负责生物系统中的强大抗菌活性,使用了生化、遗传和蛋白质组学组合测定。HPA 系统与溶液中含巯基的化合物(如半胱氨酸和还原型谷胱甘肽(GSH))反应。在原位,GSH 敲除大肠杆菌比大肠杆菌野生型对 HPA 介导的细胞死亡更敏感;GSH 补充可保护两种细菌免受 HPA 的攻击。用 HPA 处理的细菌(流感嗜血杆菌)的蛋白质组分析显示,与氧化还原和热休克相关的蛋白质被诱导。提出了 HPA 的一种新的抗菌机制,即 HPA 的活性通过 3-羟基丙醛的作用导致 GSH 和蛋白质中游离 SH-基团的消耗,导致细胞氧化还原状态失衡,最终导致细胞死亡。

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