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Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):6022-6027. doi: 10.1073/pnas.1703576114. Epub 2017 May 22.

Mechanism of H2S-mediated protection against oxidative stress in Escherichia coli.

Author information

1
Department of Genetics, State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia.
2
Department of Molecular Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia.
3
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016.
4
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016; evgeny.nudler@nyumc.org.
5
Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016.

Abstract

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 ∆sodAsodB 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.

KEYWORDS:

antibiotics; cysteine; hydrogen sulfide; oxidative stress; sulfur metabolism

PMID:
28533366
PMCID:
PMC5468659
DOI:
10.1073/pnas.1703576114
[Indexed for MEDLINE]
Free PMC Article

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