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谷氨酸脱氢酶使沙门氏菌能够在氧化应激下存活,并从巨噬细胞中清除。

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

机构信息

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.

Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, China.

出版信息

FEBS Lett. 2022 Jan;596(1):81-94. doi: 10.1002/1873-3468.14247. Epub 2021 Dec 12.

DOI:10.1002/1873-3468.14247
PMID:34855205
Abstract

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.

摘要

氧化应激和活性氧(ROS)的产生是细菌的生物威胁,这会诱导蛋白质的合成和抗氧化剂的产生以对抗它。在这里,我们报告称,沙门氏菌的谷氨酸脱氢酶(GDH)可以将铵同化到谷氨酸中,并促进谷胱甘肽(GSH)的产生,以对抗氧化损伤。氧化诱导 gdhA 的转录,该基因编码 GDH,并激活 GDH 的酶活性。ΔgdhA 突变沙门氏菌菌株的 GSH 水平降低,在巨噬细胞中的存活率降低,而通过过表达 GDH 和用其下游代谢物进行互补,可以部分恢复这种生长缺陷。因此,GDH 在氧化环境中,尤其是在低能量供应下,对沙门氏菌的生长起着至关重要的作用。

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