Mechanism of H 2 S-mediated protection against oxidative stress in Escherichia coli

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Cysteine / metabolism
  • Cystine / metabolism
  • DNA Damage / drug effects
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / metabolism
  • Hydrogen Peroxide / metabolism
  • Hydrogen Sulfide / metabolism*
  • Iron / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Sulfurtransferases / metabolism*
  • Sulfurtransferases / physiology

Substances

  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Reactive Oxygen Species
  • Cystine
  • Hydrogen Peroxide
  • Iron
  • Sulfurtransferases
  • 3-mercaptopyruvate sulphurtransferase
  • Cysteine
  • Hydrogen Sulfide