Glutamate dehydrogenase enables Salmonella to survive under oxidative stress and escape from clearance in macrophages

Glutamate dehydrogenase enables Salmonella to survive under oxidative stress and escape from clearance in macrophages
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谷氨酸脱氢酶使沙门氏菌能够在氧化应激下生存并逃避巨噬细胞的清除

DOI:
10.1002/1873-3468.14247
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发表时间:
2021-12
期刊:
影响因子:
3.5
通讯作者:
Wang Qijun
Wang Qijun
中科院分区:
生物学3区
文献类型:
--
作者:
Huang Xi;Lao Wenji;Zhou Youci;Sun Yunwei;Wang Qijun

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氧化应激和活性氧物种(ROS)的产生是细菌的一种生物威胁,它诱导蛋白质的合成和抗氧化剂的产生来对抗它。在此,我们报道了沙门氏菌的谷氨酸脱氢酶(GDH)可以将铵同化为谷氨酸,并促进谷胱甘肽(GSH)的产生,以对抗氧化损伤。氧化诱导编码谷氨酸脱氢酶的gdhA转录,激活谷氨酸脱氢酶的酶活性。ΔgdhA突变株表现出谷胱甘肽水平的降低和巨噬细胞存活率的下降,这种生长缺陷可以通过过表达GdH和与其下游代谢产物的互补来部分恢复。因此,GDH在沙门氏菌在氧化环境中的生长中起着至关重要的作用,特别是在低能量供应的情况下。
Oxidative stress and the production of reactive oxygen species (ROS) are a biological threat to bacteria, which induce the synthesis of proteins and production of antioxidants to combat it. Herein, we report that glutamate dehydrogenase (GDH) of Salmonella can assimilate ammonium into glutamate and promote the generation of glutathione (GSH) to combat oxidative damage. Oxidation induces the transcription of gdhA, which encodes GDH, and activates the enzymatic activity of GDH. The ΔgdhA mutant Salmonella strain showed decreased levels of GSH and reduced survival in macrophages, and this growth deficiency could be partially restored by overexpression of GDH and complementation with its downstream metabolites. Therefore, GDH plays a critical role in the growth of Salmonella in oxidative environments, especially under low energy supply.
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