Advertisement

Copper Toxicity

  • Marc Solioz
Chapter
Part of the SpringerBriefs in Molecular Science book series (BRIEFSMOLECULAR)

Abstract

Copper is essential for life, yet highly reactive and a potential source of cell damage. Therefore, all cells possess copper homeostatic mechanisms to keep intracellular copper at safe levels. However, under conditions of excess environmental copper, homeostatic system become overloaded and intracellular copper rises to toxic levels. Possible toxic effects of copper span a range of mechanisms and it cannot be known with certainty which mechanism is active to what extent in a particular bacterium of vast and varied bacterial world. For common laboratory species like Escherichia or Bacillus, the concept has emerged that the main toxic action of copper is the replacement of iron in iron-sulfur cluster proteins, thereby inactivating essential enzyme functions.

Keywords

Hydroxyl radical Hydrogen peroxide Fenton Glutathione Iron-sulfur cluster Thiol depletion 

References

  1. 1.
    Baureder M, Reimann R, Hederstedt L (2012) Contribution of catalase to hydrogen peroxide resistance in Enterococcus faecalis. FEMS Microbiol Lett 331:160–164CrossRefGoogle Scholar
  2. 2.
    van de Guchte M, Serror P, Chervaux C et al (2002) Stress responses in lactic acid bacteria. Antonie Van Leeuwenhoek 82:187–216CrossRefGoogle Scholar
  3. 3.
    Nandakumar R, Espirito Santo C, Madayiputhiya N et al (2011) Quantitative proteomic profiling of the Escherichia coli response to metallic copper surfaces. Biometals 24:429–444CrossRefGoogle Scholar
  4. 4.
    Yoshida Y, Furuta S, Niki E (1993) Effects of metal chelating agents on the oxidation of lipids induced by copper and iron. Biochim Biophys Acta 1210:81–88CrossRefGoogle Scholar
  5. 5.
    Woodmansee AN, Imlay JA (2003) A mechanism by which nitric oxide accelerates the rate of oxidative DNA damage in Escherichia coli. Mol Microbiol 49:11–22CrossRefGoogle Scholar
  6. 6.
    Macomber L, Rensing C, Imlay JA (2007) Intracellular copper does not catalyze the formation of oxidative DNA damage in Escherichia coli. J Bacteriol 189:1616–1626CrossRefGoogle Scholar
  7. 7.
    Changela A, Chen K, Xue Y et al (2003) Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR. Science 301:1383–1387CrossRefGoogle Scholar
  8. 8.
    Macomber L, Imlay JA (2009) The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. Proc Natl Acad Sci USA 106:8344–8349CrossRefGoogle Scholar
  9. 9.
    Chillappagari S, Seubert A, Trip H et al (2010) Copper stress affects iron homeostasis by destabilizing iron-sulfur cluster formation in Bacillus subtilis. J Bacteriol 192:2512–2524CrossRefGoogle Scholar
  10. 10.
    Fung DK, Lau WY, Chan WT et al (2013) Copper efflux is induced during anaerobic amino acid limitation in Escherichia coli to protect iron-sulfur cluster enzymes and its biogenesis. J Bacteriol 195:4556–4568CrossRefGoogle Scholar
  11. 11.
    Azzouzi A, Steunou AS, Durand A et al (2013) Coproporphyrin III excretion identifies the anaerobic coproporphyrinogen III oxidase HemN as a copper target in the Cu-ATPase mutant copA of Rubrivivax gelatinosus. Mol Microbiol 88:339–351CrossRefGoogle Scholar
  12. 12.
    Pearson RG (1968) Hard and soft acid and bases, HSAB, part I. J Chem Educ 45:581–587CrossRefGoogle Scholar
  13. 13.
    Xu FF, Imlay JA (2012) Silver(I), mercury(II), cadmium(II), and zinc(II) target exposed enzymic iron-sulfur clusters when they toxify Escherichia coli. Appl Environ Microbiol 78:3614–3621CrossRefGoogle Scholar
  14. 14.
    Park HJ, Nguyen TT, Yoon J et al (2012) Role of reactive oxygen species in Escherichia coli inactivation by cupric ion. Environ Sci Technol 46:11299–11304CrossRefGoogle Scholar
  15. 15.
    Abicht HK, Gonskikh Y, Gerber SD et al (2013) Non-enzymatic copper reduction by menaquinone enhances copper toxicity in Lactococcus lactis IL1403. Microbiol 159:1190–1197CrossRefGoogle Scholar
  16. 16.
    Ranquet C, Ollagnier-de-Choudens S, Loiseau L et al (2007) Cobalt stress in Escherichia coli. The effect on the iron-sulfur proteins. J Biol Chem 282:30442–30451CrossRefGoogle Scholar
  17. 17.
    Helbig K, Grosse C, Nies DH (2008) Cadmium toxicity in glutathione mutants of Escherichia coli. J Bacteriol 190:5439–5454CrossRefGoogle Scholar
  18. 18.
    Kimura T, Nishioka H (1997) Intracellular generation of superoxide by copper sulphate in Escherichia coli. Mutat Res 389:237–242CrossRefGoogle Scholar
  19. 19.
    Lemire JA, Harrison JJ, Turner RJ (2013) Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 11:371–384CrossRefGoogle Scholar
  20. 20.
    Newton GL, Arnold K, Price MS et al (1996) Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes. J Bacteriol 178:1990–1995CrossRefGoogle Scholar
  21. 21.
    Fahey RC, Brown WC, Adams WB et al (1978) Occurrence of glutathione in bacteria. J Bacteriol 133:1126–1129PubMedPubMedCentralGoogle Scholar
  22. 22.
    Li Y, Hugenholtz J, Abee T et al (2003) Glutathione protects Lactococcus lactis against oxidative stress. Appl Environ Microbiol 69:5739–5745CrossRefGoogle Scholar
  23. 23.
    Gaballa A, Newton GL, Antelmann H et al (2010) Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli. Proc Natl Acad Sci USA 107:6482–6486CrossRefGoogle Scholar
  24. 24.
    Kim EK, Cha CJ, Cho YJ et al (2008) Synthesis of γ-glutamylcysteine as a major low-molecular-weight thiol in lactic acid bacteria Leuconostoc spp. Biochem Biophys Res Commun 369:1047–1051CrossRefGoogle Scholar
  25. 25.
    Schafer FQ, Buettner GR (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30:1191–1212CrossRefGoogle Scholar
  26. 26.
    Obeid MH, Oertel J, Solioz M et al (2016) Mechanism of attenuation of uranyl toxicity by glutathione in Lactococcus lactis. Appl Environ Microbiol 82:3563–3571CrossRefGoogle Scholar
  27. 27.
    Fu RY, Bongers RS, van Swam II et al (2006) Introducing glutathione biosynthetic capability into Lactococcus lactis subsp. cremoris NZ9000 improves the oxidative-stress resistance of the host. Metab Eng 8:662–671CrossRefGoogle Scholar
  28. 28.
    Musci G, Di Marco S, Bellenchi GC et al (1996) Reconstitution of ceruloplasmin by the Cu(I)-glutathione complex. Evidence for a role of Mg2+ and ATP. J Biol Chem 271:1972–1978CrossRefGoogle Scholar
  29. 29.
    Ferreira AM, Ciriolo MR, Marcocci L et al (1993) Copper(I) transfer into metallothionein mediated by glutathione. Biochem J 292:673–676CrossRefGoogle Scholar
  30. 30.
    Ciriolo MR, Desideri A, Paci M et al (1990) Reconstitution of Cu, Zn-superoxide dismutase by the Cu(I).glutathione complex. J Biol Chem 265:11030–11034PubMedGoogle Scholar
  31. 31.
    Grass G, Rensing C, Solioz M (2011) Metallic copper as an antimicrobial surface. Appl Environ Microbiol 77:1541–1547CrossRefGoogle Scholar
  32. 32.
    Grass G, Hans M, Mücklich F et al (2015) Massive Kupferwerkstoffe in der Hygiene und Infektionsprävention - Zu gut um wahr zu sein? Hyg Med 40:458–463Google Scholar
  33. 33.
    Sifri CD, Burke GH, Enfield KB (2016) Reduced health care-associated infections in an acute care community hospital using a combination of self-disinfecting copper-impregnated composite hard surfaces and linens. Am J Infect Control 44:1565–1571CrossRefGoogle Scholar
  34. 34.
    Schmidt MG, von Dessauer B, Benavente C et al (2016) Copper surfaces are associated with significantly lower concentrations of bacteria on selected surfaces within a pediatric intensive care unit. Am J Infect Control 44:203–209CrossRefGoogle Scholar
  35. 35.
    Michels HT, Keevil CW, Salgado CD et al (2015) From laboratory research to a clinical trial: Copper alloy surfaces kill bacteria and reduce hospital-acquired infections. Health Environ Res Des J 9:64–79Google Scholar
  36. 36.
    Salgado CD, Sepkowitz KA, John JF et al (2013) Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol 34:479–486CrossRefGoogle Scholar
  37. 37.
    Norambuena GA, Patel R, Karau M et al (2017) Antibacterial and biocompatible titanium-copper oxide coating may be a potential strategy to reduce periprosthetic infection: an in vitro study. Clin Orthop Relat Res 475:722–732CrossRefGoogle Scholar
  38. 38.
    Humphreys H (2014) Self-disinfecting and microbiocide-impregnated surfaces and fabrics. What potential in interrupting the spread of healthcare-associated infection? Clin Infect Dis 58:848–853CrossRefGoogle Scholar
  39. 39.
    Hans M, Mathews S, Mücklich F et al (2016) Physicochemical properties of copper important for its antibacterial activity and development of a unified model. Biointerphases 11:018902-1–018902-8CrossRefGoogle Scholar
  40. 40.
    Luo J, Hein C, Mücklich F et al (2017) Killing of bacteria by copper, cadmium, and silver surfaces delineates the relevant physico-chemical parameters. Biointerphases 12:020301-1–020301-6CrossRefGoogle Scholar

Copyright information

© The Author(s) 2018

Authors and Affiliations

  1. 1.Department Clinical ResearchUniversity of BernBernSwitzerland

Personalised recommendations