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

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.

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References

  1. Barkay T, Miller SM, Summers AO (2003) FEMS Microbiol Rev 27:355–384

    CAS  Article  PubMed  Google Scholar 

  2. Mason RP, Fitzgerald WF, Morel FMM (1994) Geochim Cosmochim Acta 58:3191–3198

    CAS  Article  Google Scholar 

  3. Norn S, Permin H, Kruse E, Kruse PR (2008) Dan Medicin Arbog 36:21–40

    Google Scholar 

  4. Crinnion WJ (2000) Altern Med Rev 5:209–223

    CAS  PubMed  Google Scholar 

  5. Richardson GM, Wilson R, Allard D, Purtill C, Douma S, Graviere J (2011) Sci Total Environ 409:4257–4268

    CAS  Article  PubMed  Google Scholar 

  6. Malm O (1998) Environ Res 77:73–78

    CAS  Article  PubMed  Google Scholar 

  7. Bakir F, Damluji SF, Amin-Zaki L, Murtadha M, Khalidi A, Al-Rawi NY, Tikriti S, Dahahir HI, Clarkson TW, Smith JC, Doherty RA (1973) Science 181:230–241

    CAS  Article  PubMed  Google Scholar 

  8. Yorifuji T, Tsuda T, Takao S, Harada M (2008) Epidemiology 19:3–9

    Article  PubMed  Google Scholar 

  9. Davidson PW, Myers GJ, Weiss B (2004) Pediatrics 113:1023–1029

    PubMed  Google Scholar 

  10. Clarkson TW, Magos L (2006) Crit Rev Toxicol 36:609–662

    CAS  Article  PubMed  Google Scholar 

  11. Cheesman BV, Arnold AP, Rabenstein DL (1988) J Am Chem Soc 110:6359–6364

    CAS  Article  Google Scholar 

  12. Oram PD, Fang X, Fernando Q, Letkeman P, Letkeman D (1996) Chem Res Toxicol 9:709–712

    CAS  Article  PubMed  Google Scholar 

  13. Valko M, Morris H, Cronin MT (2005) Curr Med Chem 12:1161–1208

    CAS  Article  PubMed  Google Scholar 

  14. Schafer FQ, Buettner GR (2001) Free Radic Biol Med 30:1191–1212

    CAS  Article  PubMed  Google Scholar 

  15. Miseta A, Csutora P (2000) Mol Biol Evol 17:1232–1239

    CAS  Article  PubMed  Google Scholar 

  16. Carvalho CM, Chew EH, Hashemy SI, Lu J, Holmgren A (2008) J Biol Chem 283:11913–11923

    CAS  Article  PubMed  Google Scholar 

  17. O’Connor TR, Graves RJ, de Murcia G, Castaing B, Laval J (1993) J Biol Chem 268:9063–9070

    PubMed  Google Scholar 

  18. Imesch E, Moosmayer M, Anner BM (1992) Am J Physiol 262:F837–F842

    CAS  PubMed  Google Scholar 

  19. Soskine M, Steiner-Mordoch S, Schuldiner S (2002) Proc Natl Acad Sci USA 99:12043–12048

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  20. Khan MA, Wang F (2009) Environ Toxicol Chem 28:1567–1577

    CAS  Article  PubMed  Google Scholar 

  21. Gladyshev VN, Kryukov GV (2001) BioFactors 14:87–92

    CAS  Article  PubMed  Google Scholar 

  22. Finney LA, O’Halloran TV (2003) Science 300:931–936

    CAS  Article  PubMed  Google Scholar 

  23. Helbig K, Bleuel C, Krauss GJ, Nies DH (2008) J Bacteriol 190:5431–5438

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  24. Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Curr Top Med Chem 1:529–539

    CAS  Article  PubMed  Google Scholar 

  25. Andreini C, Bertini I, Cavallaro G, Holliday GL, Thornton JM (2008) J Biol Inorg Chem 13:1205–1218

    CAS  Article  PubMed  Google Scholar 

  26. Waldron KJ, Rutherford JC, Ford D, Robinson NJ (2009) Nature 460:823–830

    CAS  Article  PubMed  Google Scholar 

  27. Cvetkovic A, Menon AL, Thorgersen MP, Scott JW, Poole FL II, Jenney FE Jr, Lancaster WA, Praissman JL, Shanmukh S, Vaccaro BJ, Trauger SA, Kalisiak E, Apon JV, Siuzdak G, Yannone SM, Tainer JA, Adams MW (2010) Nature 466:779–782

    CAS  Article  PubMed  Google Scholar 

  28. Polacco BJ, Purvine SO, Zink EM, Lavoie SP, Lipton MS, Summers AO, Miller SM (2011) Mol Cell Proteomics 10(M110):004853

    PubMed  Google Scholar 

  29. Neidhardt FC, Bloch PL, Smith DF (1974) J Bacteriol 119:736–747

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Bradford MM (1976) Anal Biochem 72:248–254

    CAS  Article  PubMed  Google Scholar 

  31. Cayley S, Record MT Jr (2003) Biochemistry 42:12596–12609

    CAS  Article  PubMed  Google Scholar 

  32. Ellman GL (1959) Arch Biochem Biophys 82:70–77

    CAS  Article  PubMed  Google Scholar 

  33. Woodmansee AN, Imlay JA (2002) Methods Enzymol 349:3–9

    CAS  Article  PubMed  Google Scholar 

  34. Huntley RP, Sawford T, Mutowo-Meullenet P, Shypitsyna A, Bonilla C, Martin MJ, O’Donovan C (2015) Nucleic Acids Res 43:D1057–D1063

    PubMed Central  Article  PubMed  Google Scholar 

  35. Kim S, Gupta N, Pevzner PA (2008) J Proteome Res 7:3354–3363

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  36. Keller A, Nesvizhskii AI, Kolker E, Aebersold R (2002) Anal Chem 74:5383–5392

    CAS  Article  PubMed  Google Scholar 

  37. Scott RA (2000) Physical methods in bioinorganic chemistry—spectroscopy and magnetism. University Science Books, Sausalito, pp 465–504

    Google Scholar 

  38. George GN, Garrett RM, Prince RC, Rajagopalan KV (1996) J Am Chem Soc 118:8588–8592

    CAS  Article  Google Scholar 

  39. Ankudinov AL, Bouldin CE, Rehr JJ, Sims J, Hung H (2002) Phys Rev B 65

  40. Mustre de Leon J, Rehr JJ, Zabinsky SI, Albers RC (1991) Phys Rev B Condens Matter 44:4146–4156

  41. Cosper NJ, Stalhandske CM, Saari RE, Hausinger RP, Scott RA (1999) J Biol Inorg Chem 4:122–129

    CAS  Article  PubMed  Google Scholar 

  42. Tyagarajan K, Pretzer E, Wiktorowicz JE (2003) Electrophoresis 24:2348–2358

    CAS  Article  PubMed  Google Scholar 

  43. Fruchter RG, Crestfield AM (1967) J Biol Chem 242:5807–5812

    CAS  PubMed  Google Scholar 

  44. Boja ES, Fales HM (2001) Anal Chem 73:3576–3582

    CAS  Article  PubMed  Google Scholar 

  45. Cotner RC, Clagett CO (1973) Anal Biochem 54:170–177

    CAS  Article  PubMed  Google Scholar 

  46. Basinger MA, Casas J, Jones MM, Weaver AD, Weinstein NH (1981) J Inorg Nucl Chem 43:1419–1425

    CAS  Article  Google Scholar 

  47. Khokhlova A, Chernikova G, Shishin L (1982). Inst obs neorg khimii im ns kurnakova leninski prospekt 31, 71 Moscow, Russia, pp 2976–2978

  48. Powell KJ, Brown PL, Byrne RH, Gajda T, Hefter G, Sjoberg S, Wanner H (2005) IUPAC. Pure Appl Chem 77:739–800

    CAS  Article  Google Scholar 

  49. Johnson DC, Dean DR, Smith AD, Johnson MK (2005) Annu Rev Biochem 74:247–281

    CAS  Article  PubMed  Google Scholar 

  50. Keyer K, Imlay JA (1997) J Biol Chem 272:27652–27659

    CAS  Article  PubMed  Google Scholar 

  51. Lafrance-Vanasse J, Lefebvre M, Di Lello P, Sygusch J, Omichinski JG (2009) J Biol Chem 284:938–944

    CAS  Article  PubMed  Google Scholar 

  52. Parks JM, Guo H, Momany C, Liang L, Miller SM, Summers AO, Smith JC (2009) J Am Chem Soc 131:13278–13285

    CAS  Article  PubMed  Google Scholar 

  53. Xu FF, Imlay JA (2012) Appl Environ Microbiol 78:3614–3621

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  54. Stricks W, Kolthoff IM (1953) J Am Chem Soc 75:5673–5681

    CAS  Article  Google Scholar 

  55. Güzeloğlu Ş, Yalçın G, Pekin M (1998) J Organomet Chem 568:143–147

    Article  Google Scholar 

  56. McClintock CS, Parks JM, Bern M, Ghattyvenkatakrishna PK, Hettich RL (2013) J Proteome Res 12:3307–3316

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  57. Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR (2010) Proc Natl Acad Sci USA 107:19784–19789

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  58. Ferguson GP (1999) Trends Microbiol 7:242–247

    CAS  Article  PubMed  Google Scholar 

  59. Hunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H (2005) Nature 435:1197–1202

    CAS  Article  PubMed  Google Scholar 

  60. Padan E (2011) Compr Physiol 1:1711–1719

    PubMed  Google Scholar 

  61. Taglicht D, Padan E, Schuldiner S (1991) J Biol Chem 266:11289–11294

    CAS  PubMed  Google Scholar 

  62. Grass G, Otto M, Fricke B, Haney CJ, Rensing C, Nies DH, Munkelt D (2005) Arch Microbiol 183:9–18

    CAS  Article  PubMed  Google Scholar 

  63. Zheng M, Doan B, Schneider TD, Storz G (1999) J Bacteriol 181:4639–4643

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Nies DH (2003) FEMS Microbiol Rev 27:313–339

    CAS  Article  PubMed  Google Scholar 

  65. Miyake Y, Togashi H, Tashiro M, Yamaguchi H, Oda S, Kudo M, Tanaka Y, Kondo Y, Sawa R, Fujimoto T, Machinami T, Ono A (2006) J Am Chem Soc 128:2172–2173

    CAS  Article  PubMed  Google Scholar 

  66. Tanaka Y, Oda S, Yamaguchi H, Kondo Y, Kojima C, Ono A (2007) J Am Chem Soc 129:244–245

    CAS  Article  PubMed  Google Scholar 

  67. Brooks P, Davidson N (1960) J Am Chem Soc 82:2118–2123

    CAS  Article  Google Scholar 

  68. Bligh EG, Dyer WJ (1959) Can J Biochem Physiol 37:911–917

    CAS  Article  PubMed  Google Scholar 

  69. Summers AO, Wireman J, Vimy MJ, Lorscheider FL, Marshall B, Levy SB, Bennett S, Billard L (1993) Antimicrob Agents Chemother 37:825–834

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  70. Rietschel RL, Wilson LA (1982) Arch Dermatol 118:147–149

    CAS  Article  PubMed  Google Scholar 

  71. Tosti A, Tosti G (1988) Contact Dermatitis 18:268–273

    CAS  Article  PubMed  Google Scholar 

  72. Freed LF (1948) S Afr Med J 22:223–229

    CAS  PubMed  Google Scholar 

  73. Weed LE, Ecker EE (1931) J Infect Dis 49:440–449

  74. Ball LK, Ball R, Pratt RD (2001) Pediatrics 107:1147–1154

    CAS  Article  PubMed  Google Scholar 

  75. WHO (2002) Wkly Epidemiol Rec 77:305–316

  76. Gutknecht J (1981) J Membr Biol 61:61–66

    CAS  Article  Google Scholar 

  77. Barkay T, Gillman M, Turner RR (1997) Appl Environ Microbiol 63:4267–4271

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Owens RA, Hartman PE (1986) J Bacteriol 168:109–114

    PubMed Central  CAS  PubMed  Google Scholar 

  79. Eser M, Masip L, Kadokura H, Georgiou G, Beckwith J (2009) Proc Natl Acad Sci USA 106:1572–1577

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  80. Ndu U, Mason RP, Zhang H, Lin S, Visscher PT (2012) Appl Environ Microbiol 78:7276–7282

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  81. Mah V, Jalilehvand F (2008) J Biol Inorg Chem 13:541–553

    CAS  Article  PubMed  Google Scholar 

  82. Ravichandran M (2004) Chemosphere 55:319–331

    CAS  Article  PubMed  Google Scholar 

  83. Imlay JA (2013) Nat Rev Microbiol 11:443–454

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  84. Ledwidge R, Patel B, Dong A, Fiedler D, Falkowski M, Zelikova J, Summers AO, Pai EF, Miller SM (2005) Biochemistry 44:11402–11416

    CAS  Article  PubMed  Google Scholar 

  85. Jung YS, Yu L, Golbeck JH (1995) Photosynth Res 46:249–255

    CAS  Article  PubMed  Google Scholar 

  86. Roche B, Aussel L, Ezraty B, Mandin P, Py B, Barras F (2013) Biochim Biophys Acta 1827:455–469

    CAS  Article  PubMed  Google Scholar 

  87. Hong B, Nauss R, Harwood IM, Miller SM (2010) Biochemistry 49:8187–8196

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  88. Gabriel SE, Helmann JD (2009) J Bacteriol 191:6116–6122

    PubMed Central  CAS  Article  PubMed  Google Scholar 

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Acknowledgments

We thank Mary Lipton, Erika Zink, and Samuel Purvine (all of the DOE Pacific Northwest National Laboratory) for chemical and biophysical acquisition and SEQUEST analysis of the proteomic data, Tejas Chaudhari and Sagar Tarkhadkar (Department of Computer Sciences, Univ. of Georgia) for assistance with database development and management, and Graham George (University of Saskatchewan and the Canadian Light Source) for mercuric bromide EXAFS data collection. This work was supported by DOE awards ER64408 and ER65286 to AOS and ER64409 and ER65195 to SMM and NIH award GM62524 to MKJ.

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Correspondence to Anne O. Summers.

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LaVoie, S.P., Mapolelo, D.T., Cowart, D.M. et al. Organic and inorganic mercurials have distinct effects on cellular thiols, metal homeostasis, and Fe-binding proteins in Escherichia coli . J Biol Inorg Chem 20, 1239–1251 (2015). https://doi.org/10.1007/s00775-015-1303-1

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  • DOI: https://doi.org/10.1007/s00775-015-1303-1

Keywords

  • Metal toxicity
  • Electrolyte balance
  • Proteomics
  • EPR
  • EXAFS