JBIC Journal of Biological Inorganic Chemistry

, Volume 20, Issue 8, pp 1239–1251 | Cite as

Organic and inorganic mercurials have distinct effects on cellular thiols, metal homeostasis, and Fe-binding proteins in Escherichia coli

  • Stephen P. LaVoie
  • Daphne T. Mapolelo
  • Darin M. Cowart
  • Benjamin J. Polacco
  • Michael K. Johnson
  • Robert A. Scott
  • Susan M. Miller
  • Anne O. Summers
Original Paper

Abstract

The protean chemical properties of the toxic metal mercury (Hg) have made it attractive in diverse applications since antiquity. However, growing public concern has led to an international agreement to decrease its impact on health and the environment. During a recent proteomics study of acute Hg exposure in E. coli, we also examined the effects of inorganic and organic Hg compounds on thiol and metal homeostases. On brief exposure, lower concentrations of divalent inorganic mercury Hg(II) blocked bulk cellular thiols and protein-associated thiols more completely than higher concentrations of monovalent organomercurials, phenylmercuric acetate (PMA) and merthiolate (MT). Cells bound Hg(II) and PMA in excess of their available thiol ligands; X-ray absorption spectroscopy indicated nitrogens as likely additional ligands. The mercurials released protein-bound iron (Fe) more effectively than common organic oxidants and all disturbed the Na+/K+ electrolyte balance, but none provoked efflux of six essential transition metals including Fe. PMA and MT made stable cysteine monothiol adducts in many Fe-binding proteins, but stable Hg(II) adducts were only seen in CysXxx(n)Cys peptides. We conclude that on acute exposure: (a) the distinct effects of mercurials on thiol and Fe homeostases reflected their different uptake and valences; (b) their similar effects on essential metal and electrolyte homeostases reflected the energy dependence of these processes; and (c) peptide phenylmercury-adducts were more stable or detectable in mass spectrometry than Hg(II)-adducts. These first in vivo observations in a well-defined model organism reveal differences upon acute exposure to inorganic and organic mercurials that may underlie their distinct toxicology.

Keywords

Metal toxicity Electrolyte balance Proteomics EPR EXAFS 

Supplementary material

775_2015_1303_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1856 kb)

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Copyright information

© SBIC 2015

Authors and Affiliations

  • Stephen P. LaVoie
    • 1
  • Daphne T. Mapolelo
    • 2
    • 3
  • Darin M. Cowart
    • 2
  • Benjamin J. Polacco
    • 4
  • Michael K. Johnson
    • 2
  • Robert A. Scott
    • 2
  • Susan M. Miller
    • 4
  • Anne O. Summers
    • 1
  1. 1.Department of MicrobiologyUniversity of GeorgiaAthensUSA
  2. 2.Department of ChemistryUniversity of GeorgiaAthensUSA
  3. 3.Department of ChemistryUniversity of BotswanaGaboroneBotswana
  4. 4.Department of Pharmaceutical ChemistryUniversity of California San FranciscoSan FranciscoUSA

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