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标题：Mechanism of H2S-mediated protection against oxidative stress in Escherichia coli
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作者：Alexander Mironov ; Tatyana Seregina ; Maxim Nagornykh 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：23
页码：6022-6027
DOI：10.1073/pnas.1703576114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Endogenous hydrogen sulfide (H₂S) renders bacteria highly resistant to oxidative stress, but its mechanism remains poorly understood. Here, we report that 3-mercaptopyruvate sulfurtransferase (3MST) is the major source of endogenous H₂S in Escherichia coli . Cellular resistance to H₂O₂ strongly depends on the activity of mstA , a gene that encodes 3MST. Deletion of the ferric uptake regulator (Fur) renders ∆ mstA cells hypersensitive to H₂O₂. Conversely, induction of chromosomal mstA from a strong pLtetO-1 promoter (P_tet- mstA ) renders ∆ fur cells fully resistant to H₂O₂. Furthermore, the endogenous level of H₂S is reduced in ∆ fur or ∆ sodA ∆ sodB cells but restored after the addition of an iron chelator dipyridyl. Using a highly sensitive reporter of the global response to DNA damage (SOS) and the TUNEL assay, we show that 3MST-derived H₂S protects chromosomal DNA from oxidative damage. We also show that the induction of the CysB regulon in response to oxidative stress depends on 3MST, whereas the CysB-regulated l -cystine transporter, TcyP, plays the principle role in the 3MST-mediated generation of H₂S. These findings led us to propose a model to explain the interplay between l -cysteine metabolism, H₂S production, and oxidative stress, in which 3MST protects E. coli against oxidative stress via l -cysteine utilization and H₂S-mediated sequestration of free iron necessary for the genotoxic Fenton reaction.
关键词：hydrogen sulfide ; oxidative stress ; cysteine ; sulfur metabolism ; antibiotics