Organic and inorganic mercurials have distinct effects on cellular thiols, metal homeostasis, and Fe-binding proteins in Escherichia coli.
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.
Department of Microbiology, University of Georgia, Athens, GA, 30602, USA.
Stephen P
SP
LaVoie
Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.|Department of Chemistry, University of Botswana, P.O. Box 00704, Gaborone, Botswana.
Daphne T
DT
Mapolelo
Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.
Darin M
DM
Cowart
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94158, USA.
Benjamin J
BJ
Polacco
Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.
Michael K
MK
Johnson
Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.
Robert A
RA
Scott
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94158, USA.
Susan M
SM
Miller
Department of Microbiology, University of Georgia, Athens, GA, 30602, USA. summers@uga.edu.
Anne O
AO
Summers
D004578:Electron Spin Resonance Spectroscopy; D004785:Environmental Pollutants / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects*; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008628:Mercury / Q000494:pharmacology* / Q000633:toxicity*; D009941:Organomercury Compounds / Q000633:toxicity; D013438:Sulfhydryl Compounds
D004785:Environmental Pollutants; D033862:Iron-Binding Proteins; D009941:Organomercury Compounds; D013438:Sulfhydryl Compounds; D008628:Mercury
EPR; EXAFS; Electrolyte balance; Metal toxicity; Proteomics