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Antimicrobial activity of metals: mechanisms, molecular targets and applications

Key Points

  • The field of metal toxicology is vast, and although a wealth of information exists to account for bacterial resistance mechanisms towards metals, much less is known about the molecular and cellular targets of toxic metals in microorganisms.

  • Every metal atom has chemical properties that give rise to characteristic interactions with donor ligands, including reduction potential and metal speciation, both within cells and in the extracellular environment. These are key determinants of microbial toxicity.

  • Metal uptake is an important first step for poisoning. Bacterial uptake of non-essential metals occurs through routes normally reserved for essential organic and inorganic ions, and transporters from several families are now known to be involved.

  • Recent advances have begun to define the mechanisms of antimicrobial metal toxicity. These include the production of reactive oxygen species and free radicals, and the depletion of antioxidants; protein dysfunction and loss of enzyme activity; damage to cellular membranes and disruption of electron transport; interference with nutrient acquisition; and genotoxicity.

  • Our increased understanding of microbial metal toxicology is ushering in a new era for the rational design of metal-based antimicrobial agents. New innovations include antibacterial metal nanoparticles, abiotic metal surfaces and coatings, and the use of siderophores as delivery vehicles for toxic metals.

  • Metal-based antimicrobial therapies hold great promise as alternatives to antibiotics, but their potential for toxicity limits their applications. Care should be taken to protect human health and to minimize the damage that might occur to natural ecosystems as a result of the commercial use of metal-based antimicrobial technology.

Abstract

Metals have been used as antimicrobial agents since antiquity, but throughout most of history their modes of action have remained unclear. Recent studies indicate that different metals cause discrete and distinct types of injuries to microbial cells as a result of oxidative stress, protein dysfunction or membrane damage. Here, we describe the chemical and toxicological principles that underlie the antimicrobial activity of metals and discuss the preferences of metal atoms for specific microbial targets. Interdisciplinary research is advancing not only our understanding of metal toxicity but also the design of metal-based compounds for use as antimicrobial agents and alternatives to antibiotics.

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Figure 1: Hard–soft acid base (HSAB) theory can predict the selectivity of metal ions for biological donor ligands.
Figure 2: Antibacterial mechanisms of metal toxicity.
Figure 3: Metallic nanomaterials: engineered antimicrobial weaponry.

References

  1. Waldron, K. J. & Robinson, N. J. How do bacterial cells ensure that metalloproteins get the correct metal? Nature Rev. Microbiol. 7, 25–35 (2009).

    Article  CAS  Google Scholar 

  2. Andreini, C., Bertini, I. & Rosato, A. A hint to search for metalloproteins in gene banks. Bioinformatics 20, 1373–1380 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Harrison, J. J., Ceri, H., Stremick, C. & Turner, R. J. Biofilm susceptibility to metal toxicity. Environ. Microbiol. 6, 1220–1227 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Nies, D. H. Microbial heavy-metal resistance. Appl. Microbiol. Biotechnol. 51, 730–750 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Afessa, B. et al. Association between a silver-coated endotracheal tube and reduced mortality in patients with ventilator-associated pneumonia. Chest 137, 1015–1021 (2010).

    Article  PubMed  Google Scholar 

  6. Kollef, M. H. et al. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA 300, 805–813 (2008). A large-scale, multicentre clinical trial showing that patients receiving Ag-coated endotracheal tubes had a significant reduction in the incidence of ventilator-associated pneumonia.

    Article  CAS  PubMed  Google Scholar 

  7. Saint, S., Elmore, J. G., Sullivan, S. D., Emerson, S. S. & Koepsell, T. D. The efficacy of silver alloy-coated urinary catheters in preventing urinary tract infection: a meta-analysis. Am. J. Med. 105, 236–241 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Banin, E. et al. The potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent. Proc. Natl Acad. Sci. USA 105, 16761–16766 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kaneko, Y., Theondel, M., Olakanmi, O., Britigan, B. E. & Singh, P. K. The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J. Clin. Invest. 117, 877–888 (2007). A paper describing how Ga interferes with Fe sensing in P. aeruginosa.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Harrison, J. J. et al. Copper and quaternary ammonium cations exert synergistic bactericidal and anti-biofilm activity against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52, 2870–2881 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Middaugh, J. et al. Aluminum triggers decreased aconitase activity via Fe-S cluster disruption and the overexpression of isocitrate dehydrogenase and isocitrate lyase: a metabolic network mediating cellular survival. J. Biol. Chem. 280, 3159–3165 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Macomber, L., Elsey, S. P. & Hausinger, R. P. Fructose-1,6-bisphosphate aldolase (class II) is the primary site of nickel toxicity in Escherichia coli. Mol. Microbiol. 82, 1291–1300 (2011). A study that correlates bacteriostasis to Ni-dependent inhibition of a glycolytic enzyme in E. coli.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Macomber, L. & Imlay, J. A. The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. Proc. Natl Acad. Sci. USA 106, 8344–8349 (2009). Work which demonstrates that Cu abolishes the activity of sensitive enzymes with solvent-accessible Fe–S clusters and that this is responsible for growth inhibition of E. coli.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wright, J. B., Lam, K. & Burell, R. E. Wound management in an era of increasing bacterial antibiotic resistance: a role for topical silver treatment. Am. J. Infect. Control 26, 572–577 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Mikolay, A. et al. Survival of bacteria on metallic copper surfaces in a hospital trial. Appl. Microbiol. Biotechnol. 87, 1875–1879 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Haas, K. L. & Franz, K. J. Application of metal coordination chemistry to explore and manipulate cell biology. Chem. Rev. 109, 4921–4960 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ma, Z., Jacobsen, F. E. & Giedroc, D. P. Coordination chemistry of bacterial metal transport and sensing. Chem. Rev. 109, 4644–4681 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Finney, L. A. & O'Halloran, T. V. Transition metal speciation in the cell: insights from the chemistry of metal ion receptors. Science 300, 931–936 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. Irving, H. & Williams, R. J. P. The stability of transition-metal complexes. J. Chem. Soc. 1953, 3192–3210 (1953).

    Article  Google Scholar 

  20. Waldron, K. J., Rutherford, J. C., Ford, D. & Robinson, N. J. Metalloproteins and metal sensing. Nature 460, 823–830 (2009).

    Article  CAS  PubMed  Google Scholar 

  21. Elias, M. et al. The molecular basis of phosphate discrimination in arsenate-rich environments. Nature 491, 134–137 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Clarkson, T. W. Molecular and ionic mimicry of toxic metals. Annu. Rev. Pharmacol. Toxicol. 33, 545–571 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Jennette, K. W. The role of metals in carcinogenesis: biochemistry and metabolism. Environ. Health Perspect. 40, 233–252 (1981). The first definition of ionic and molecular mimicry in the field of toxicology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pearson, R. G. Hard and soft acids and bases. J. Am. Chem. Soc. 85, 3533–3539 (1963). A landmark description of the preferences of metal ions for different types of donor ligands.

    Article  CAS  Google Scholar 

  25. Parr, R. G. & Pearson, R. G. Absolute hardness: companion parameter to absolute electronegativity. J. Am. Chem. Soc. 105, 7512–7516 (1983).

    Article  CAS  Google Scholar 

  26. Workentine, M. L., Harrison, J. J., Stenroos, P. U., Ceri, H. & Turner, R. J. Pseudomonas fluorescens' view of the periodic table. Environ. Microbiol. 10, 238–250 (2008). A study that establishes statistical correlations between the microbiological toxicity of metal ions and their chemical properties.

    CAS  PubMed  Google Scholar 

  27. Nies, D. H. Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol. Rev. 27, 313–339 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. Harrison, J. J., Ceri, H. & Turner, R. J. Multimetal resistance and tolerance in microbial biofilms. Nature Rev. Microbiol. 5, 928–938 (2007).

    Article  CAS  Google Scholar 

  29. Stewart, E. J., Aslund, F. & Beckwith, J. Disulfide bond formation in the Escherichia coli cytoplasm: an in vivo role reversal for the thioredoxins. EMBO J. 17, 5543–5550 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gadd, G. M. Metals, minerals and microbes: geomicrobiology and bioremediation. Microbiology 156, 609–643 (2010).

    Article  CAS  PubMed  Google Scholar 

  31. Cornelis, G., Johnson, C. A., Gerven, T. V. & Vandecasteele, C. Leaching mechanisms of oxyanionic metalloid and metal species in alkaline solid wastes: a review. Appl. Geochem. 23, 955–976 (2008).

    Article  CAS  Google Scholar 

  32. Allen, H. E., Hall, R. H. & Brisbin, T. D. Metal speciation: effects on aquatic toxicity. Environ. Sci. Technol. 14, 441–443 (1980).

    Article  CAS  PubMed  Google Scholar 

  33. Allen, H. E. & Hansen, D. J. The importance of trace metal speciation to water quality criteria. Water Environ. Res. 68, 42–54 (1996).

    Article  CAS  Google Scholar 

  34. Saier, M. H. Jr, Tran, C. V. & Barabote, R. D. TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Res. 34, D181–D186 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Schue, M., Dover, L. G., Besra, G. S., Parkhill, J. & Brown, N. L. Sequence and analysis of a plasmid-encoded mercury resistance operon from Mycobacterium marinum identifies MerH, a new mercuric ion transporter. J. Bacteriol. 191, 439–444 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Barkay, T., Miller, S. M. & Summers, A. O. Bacterial mercury resistance from atoms to ecosystems. FEMS Microbiol. Rev. 27, 355–384 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Lopez, M. L., Garcia-Gimenez, E., Aguilella, V. M. & Alcaraz, A. Critical assessment of OmpF channel selectivity: merging information from different experimental protocols. J. Phys. Condens. Matter 22, 454106 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Hohle, T. H., Franck, W. L., Stacey, G. & O'Brian, M. R. Bacterial outer membrane channel for divalent metal ion acquisition. Proc. Natl Acad. Sci. USA 108, 15390–15395 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Makui, H. et al. Identification of the Escherichia coli K-12 Nramp orthologue (MntH) as a selective divalent metal ion transporter. Mol. Microbiol. 35, 1065–1078 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Feng, Q. L. et al. A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J. Biomed. Mater. Res. 52, 662–668 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Cohen, A., Nelson, H. & Nelson, N. The family of SMF metal ion transporters in yeast cells. J. Biol. Chem. 275, 33388–33394 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Grass, G. et al. The metal permease ZupT from Escherichia coli is a transporter with a broad substrate spectrum. J. Bacteriol. 187, 1604–1611 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lin, W., Chai, J., Love, J. & Fu, D. Selective electrodiffusion of zinc ions in a Zrt-, Irt-like protein, ZIPB. J. Biol. Chem. 285, 39013–39020 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Anderson, D. S., Adhikari, P., Nowalk, A. J., Chen, C. Y. & Mietzner, T. A. The hFbpABC transporter from Haemophilus influenzae functions as a binding-protein-dependent ABC transporter with high specificity and affinity for ferric iron. J. Bacteriol. 186, 6220–6229 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hao, Z., Chen, S. & Wilson, D. B. Cloning, expression, and characterization of cadmium and manganese uptake genes from Lactobacillus plantarum. Appl. Environ. Microbiol. 65, 4746–4752 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Sanders, O. I., Rensing, C., Kuroda, M., Mitra, B. & Rosen, B. P. Antimonite is accumulated by the glycerol facilitator GlpF in Escherichia coli. J. Bacteriol. 179, 3365–3367 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Meng, Y. L., Liu, Z. & Rosen, B. P. As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli. J. Biol. Chem. 279, 18334–18341 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Wysocki, R. et al. The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae. Mol. Microbiol. 40, 1391–1401 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Pereira, Y. et al. Chromate causes sulfur starvation in yeast. Toxicol. Sci. 106, 400–412 (2008).

    Article  CAS  PubMed  Google Scholar 

  50. Borghese, R. & Zannoni, D. Acetate permease (ActP) Is responsible for tellurite (TeO32−) uptake and resistance in cells of the facultative phototroph Rhodobacter capsulatus. Appl. Environ. Microbiol. 76, 942–944 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Elias, A. O. et al. Tellurite enters Escherichia coli mainly through the PitA phosphate transporter. Microbiologyopen 1, 259–267 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Willsky, G. R. & Malamy, M. H. Effect of arsenate on inorganic phosphate transport in Escherichia coli. J. Bacteriol. 144, 366–374 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Hussein, S., Hantke, K. & Braun, V. Citrate-dependent iron transport system in Escherichia coli K-12. Eur. J. Biochem. 117, 431–437 (1981).

    Article  CAS  PubMed  Google Scholar 

  54. Jensen, L. T., Ajua-Alemanji, M. & Culotta, V. C. The Saccharomyces cerevisiae high affinity phosphate transporter encoded by PHO84 also functions in manganese homeostasis. J. Biol. Chem. 278, 42036–42040 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Beard, S. J. et al. Evidence for the transport of zinc(II) ions via the pit inorganic phosphate transport system in Escherichia coli. FEMS Microbiol. Lett. 184, 231–235 (2000).

    Article  CAS  PubMed  Google Scholar 

  56. Schaefer, J. K. & Morel, F. M. M. High methylation rates of mercury bound to cysteine by Geobacter sulfurreducens. Nature Geosci. 2, 123–126 (2009).

    Article  CAS  Google Scholar 

  57. Bellenger, J. P., Wichard, T., Kustka, A. B. & Kraepiel, A. M. L. Uptake of molybdenum and vanadium by a nitrogen-fixing soil bacterium using siderophores. Nature Geosci. 1, 243–246 (2008).

    Article  CAS  Google Scholar 

  58. Schalk, I. J., Hannauer, M. & Braud, A. New roles for bacterial siderophores in metal transport and tolerance. Environ. Microbiol. 13, 2844–2854 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Braud, A., Hannauer, M., Mislin, G. L. & Schalk, I. J. The Pseudomonas aeruginosa pyochelin-iron uptake pathway and its metal specificity. J. Bacteriol. 191, 3517–3525 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hannauer, M. et al. The PvdRT-OpmQ efflux pump controls the metal selectivity of the iron uptake pathway mediated by the siderophore pyoverdine in Pseudomonas aeruginosa. Environ. Microbiol. 14, 1696–1708 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Braud, A., Hoegy, F., Jezequel, K., Lebeau, T. & Schalk, I. J. New insights into the metal specificity of the Pseudomonas aeruginosa pyoverdine–iron uptake pathway. Environ. Microbiol. 11, 1079–1091 (2009).

    Article  CAS  PubMed  Google Scholar 

  62. Imlay, J. A., Chin, S. M. & Linn, S. Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 240, 640–642 (1988).

    Article  CAS  PubMed  Google Scholar 

  63. Macomber, L., Rensing, C. & Imlay, J. A. Intracellular copper does not catalyze the formation of oxidative DNA damage in Escherichia coli. J. Bacteriol. 189, 1616–1626 (2007). Research demonstrating that Cu catalyses the formation of the hydroxyl radical in vivo and suggests that this chemistry is localized to the periplasmic space of E. coli.

    Article  CAS  PubMed  Google Scholar 

  64. Harrison, J. J. et al. Chromosomal antioxidant genes have metal ion-specifc roles as determinants of bacterial metal tolerance. Environ. Microbiol. 11, 2491–2509 (2009).

    Article  CAS  PubMed  Google Scholar 

  65. Perez, J. M. et al. Bacterial toxicity of potassium tellurite: unveiling an ancient enigma. PLoS ONE 2, e211 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Nunoshiba, T. et al. Role of iron and superoxide for generation of hydroxyl radical, oxidative DNA lesions, and mutagenesis in Escherichia coli. J. Biol. Chem. 274, 34832–34837 (1999).

    Article  CAS  PubMed  Google Scholar 

  67. Touati, D., Jacques, M., Tardat, B., Bouchard, L. & Despied, S. Lethal oxidative damage and mutagenesis are generated by iron in Δfur mutants of Escherichia coli: protective role of superoxide dismutase. J. Bacteriol. 177, 2305–2314 (1995). A report that links Fe toxicity to lethal DNA damage in E. coli.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Warnes, S. L. & Keevil, C. W. Mechanism of copper surface toxicity in vancomycin-resistant enterococci following wet or dry surface contact. Appl. Environ. Microbiol. 77, 6049–6059 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Warnes, S. L., Caves, V. & Keevil, C. W. Mechanism of copper surface toxicity in Escherichia coli O157:H7 and Salmonella involves immediate membrane depolarization followed by slower rate of DNA destruction which differs from that observed for Gram-positive bacteria. Environ. Microbiol. 14, 1730–1743 (2012).

    Article  CAS  PubMed  Google Scholar 

  70. Imlay, J. A. Pathways of oxidative damage. Annu. Rev. Microbiol. 57, 395–418 (2003). The definitive review of O toxicity in bacteria.

    Article  CAS  PubMed  Google Scholar 

  71. Itoh, M. et al. Mechanism of chromium(VI) toxicity in Escherichia coli: is hydrogen peroxide essential in Cr(VI) toxicity? J. Biochem. 117, 780–786 (1995).

    Article  CAS  PubMed  Google Scholar 

  72. Geslin, C., Llanos, J., Prieur, D. & Jeanthon, C. The manganese and iron superoxide dismutases protect Escherichia coli from heavy metal toxicity. Res. Microbiol. 152, 901–905 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Parvatiyar, K. et al. Global analysis of cellular factors and responses involved in Pseudomonas aeruginosa resistance to arsenite. J. Bacteriol. 187, 4853–4864 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Sumner, E. R. et al. Oxidative protein damage causes chromium toxicity in yeast. Microbiology 151, 1939–1948 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Calderon, I. L. et al. Tellurite-mediated disabling of [4Fe–4S] clusters of Escherichia coli dehydratases. Microbiology 155, 1840–1846 (2009).

    Article  CAS  PubMed  Google Scholar 

  76. Teitzel, G. M. et al. Survival and growth in the presence of elevated copper: transcriptional profiling of copper-stressed Pseudomonas aeruginosa. J. Bacteriol. 188, 7242–7256 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Jin, Y. H. et al. Global transcriptome and deletome profiles of yeast exposed to transition metals. PLoS Genet. 4, e1000053 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Valko, M., Morris, H. & Cronin, M. T. D. Metals, toxicity and oxidative stress. Curr. Med. Chem. 12, 1161–1208 (2005). A comprehensive summary of in vitro metal chemistry and its relationship to toxicology.

    Article  CAS  PubMed  Google Scholar 

  79. Stohs, S. J. & Bagchi, D. Oxidative mechanisms in the toxicity of metal ions. Free Radic. Biol. Med. 18, 321–336 (1995).

    Article  CAS  PubMed  Google Scholar 

  80. Faulkner, M. J. & Helmann, J. D. Peroxide stress elicits adaptive changes in bacterial metal ion homeostasis. Antioxid. Redox Signal. 15, 175–189 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Strlič, M., Kolar, J., Šelih, V.-S., Kočar, D. & Pihlar, B. A comparative study of several transition metals in Fenton-like reaction systems at circum-neutral pH. Acta Chim. Slov. 50, 619–632 (2003).

    Google Scholar 

  82. Barnese, K., Gralla, E. B., Valentine, J. S. & Cabelli, D. E. Biologically relevant mechanism for catalytic superoxide removal by simple manganese compounds. Proc. Natl Acad. Sci. USA 109, 6892–6897 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Anjem, A. & Imlay, J. A. Mononuclear iron enzymes are primary targets of hydrogen peroxide stress. J. Biol. Chem. 287, 15544–15556 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Anjem, A., Varghese, S. & Imlay, J. A. Manganese import is a key element of the OxyR response to hydrogen peroxide in Escherichia coli. Mol. Microbiol. 72, 844–858 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Xu, F. F. & Imlay, J. A. Silver(I), mercury(II), cadmium(II), and zinc(II) target exposed enzymic iron-sulfur clusters when they toxify Escherichia coli. Appl. Environ. Microbiol. 78, 3614–3621 (2012). Work which demonstrates that soft metals may be toxic because they destroy the Fe–S clusters of dehydratases in E. coli.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Outten, C. E. & O'Halloran, T. V. Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis. Science 292, 2488–2492 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Keyer, K. & Imlay, J. A. Superoxide accelerates DNA damage by elevating free-iron levels. Proc. Natl Acad. Sci. USA 93, 13635–13640 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xu, H. et al. Role of reactive oxygen species in the antibacterial mechanism of silver nanoparticles on Escherichia coli O157:H7. Biometals 25, 45–53 (2012).

    Article  CAS  PubMed  Google Scholar 

  89. Park, H. J. et al. Silver-ion-mediated reactive oxygen species generation affecting bactericidal activity. Water Res. 43, 1027–1032 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Gordon, O. et al. Silver coordination polymers for prevention of implant infection: thiol interaction, impact on respiratory chain enzymes, and hydroxyl radical induction. Antimicrob. Agents Chemother. 54, 4208–4218 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Stojiljkovic, I., Kumar, V. & Srinivasan, N. Non-iron metalloporphyrins: potent antibacterial compounds that exploit haem/Hb uptake systems of pathogenic bacteria. Mol. Microbiol. 31, 429–442 (1999).

    Article  CAS  PubMed  Google Scholar 

  92. Valko, M., Rhodes, C. J., Moncol, J., Izakovic, M. & Mazur, M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 160, 1–40 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Helbig, K., Grosse, C. & Nies, D. H. Cadmium toxicity in glutathione mutants of Escherichia coli. J. Bacteriol. 190, 5439–5454 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Helbig, K., Bleuel, C., Krauss, G. J. & Nies, D. H. Glutathione and transition-metal homeostasis in Escherichia coli. J. Bacteriol. 190, 5431–5438 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Liau, S. Y., Read, D. C., Pugh, W. J., Furr, J. R. & Russell, A. D. Interaction of silver nitrate with readily identifiable groups: relationship to the antibacterial action of silver ions. Lett. Appl. Microbiol. 25, 279–283 (1997).

    Article  CAS  PubMed  Google Scholar 

  96. Fauchon, M. et al. Sulfur sparing in the yeast proteome in response to sulfur demand. Mol. Cell 9, 713–723 (2002). A study that identifies the S-sparing response in S. cerevisiae as a mechanism to cope with Cd toxicity.

    Article  CAS  PubMed  Google Scholar 

  97. Stadtman, E. R. & Levine, R. L. Free radical-mediated oxidation of free amino acids and amino acid residues in proteins. Amino Acids 25, 207–218 (2003).

    Article  CAS  PubMed  Google Scholar 

  98. Stadtman, E. R. Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions. Annu. Rev. Biochem. 62, 797–821 (1993).

    Article  CAS  PubMed  Google Scholar 

  99. Erskine, P. T. et al. X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase. Nature Struct. Biol. 4, 1025–1031 (1997). A paper that defines the structural basis for the replacement of Zn by Pb at the active site of ALAD.

    Article  CAS  PubMed  Google Scholar 

  100. Ogunseitan, O. A., Yang, S. & Ericson, J. Microbial δ-aminolevulinate dehydratase as a biosensor of lead bioavailability in contaminated environments. Soil Biol. Biochem. 32, 1899–1906 (2000).

    Article  CAS  Google Scholar 

  101. Ciriolo, M. R. et al. Purification and characterization of Ag, Zn-superoxide dismutase from Saccharomyces cerevisiae exposed to silver. J. Biol. Chem. 269, 25783–25787 (1994).

    CAS  PubMed  Google Scholar 

  102. Zhang, Y. M. & Rock, C. O. Membrane lipid homeostasis in bacteria. Nature Rev. Microbiol. 6, 222–233 (2008).

    Article  CAS  Google Scholar 

  103. Li, W. R. et al. Antibacterial activity and mechanism of silver nanoparticles on Escherichia coli. Appl. Microbiol. Biotechnol. 85, 1115–1122 (2010).

    Article  CAS  PubMed  Google Scholar 

  104. Jung, W. K. et al. Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl. Environ. Microbiol. 74, 2171–2178 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Yamanaka, M., Hara, K. & Kudo, J. Bactericidal actions of a silver ion solution on Escherichia coli, studied by energy-filtering transmission electron microscopy and proteomic analysis. Appl. Environ. Microbiol. 71, 7589–7593 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Yaganza, E. S., Rioux, D., Simard, M., Arul, J. & Tweddell, R. J. Ultrastructural alterations of Erwinia carotovora subsp. atroseptica caused by treatment with aluminum chloride and sodium metabisulfite. Appl. Environ. Microbiol. 70, 6800–6808 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Lok, C. N. et al. Proteomic analysis of the mode of antibacterial action of silver nanoparticles. J. Proteome Res. 5, 916–924 (2006).

    Article  CAS  PubMed  Google Scholar 

  108. Bragg, P. D. & Rainnie, D. J. The effect of silver ions on the respiratory chain of Escherichia coli. Can. J. Microbiol. 20, 883–889 (1974).

    Article  CAS  PubMed  Google Scholar 

  109. Fadeeva, M. S., Bertsova, Y. V., Euro, L. & Bogachev, A. V. Cys377 residue in NqrF subunit confers Ag+ sensitivity of Na+-translocating NADH:quinone oxidoreductase from Vibrio harveyi. Biochemistry 76, 186–195 (2011).

    CAS  PubMed  Google Scholar 

  110. Dibrov, P., Dzioba, J., Gosink, K. K. & Hase, C. C. Chemiosmotic mechanism of antimicrobial activity of Ag+ in Vibrio cholerae. Antimicrob. Agents Chemother. 46, 2668–2670 (2002). Evidence that Ag cations induce massive leakage of protons through membranes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hong, R., Kang, T. Y., Michels, C. A. & Gadura, N. Membrane lipid peroxidation in copper alloy-mediated contact killing of Escherichia coli. Appl. Environ. Microbiol. 78, 1776–1784 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Howlett, N. G. & Avery, S. V. Induction of lipid peroxidation during heavy metal stress in Saccharomyces cerevisiae and influence of plasma membrane fatty acid unsaturation. Appl. Environ. Microbiol. 63, 2971–2976 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Grass, G., Rensing, C. & Solioz, M. Metallic copper as an antimicrobial surface. Appl. Environ. Microbiol. 77, 1541–1547 (2011).

    Article  CAS  PubMed  Google Scholar 

  114. Janero, D. R. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic. Biol. Med. 9, 515–540 (1990).

    Article  CAS  PubMed  Google Scholar 

  115. Linley, E., Denyer, S. P., McDonnell, G., Simons, C. & Maillard, J. Y. Use of hydrogen peroxide as a biocide: new consideration of its mechanisms of biocidal action. J. Antimicrob. Chemother. 67, 1589–1596 (2012).

    Article  CAS  PubMed  Google Scholar 

  116. Nishioka, H. Mutagenic activities of metal compounds in bacteria. Mutat. Res. 31, 185–189 (1975).

    Article  CAS  PubMed  Google Scholar 

  117. Green, M. H., Muriel, W. J. & Bridges, B. A. Use of a simplified fluctuation test to detect low levels of mutagens. Mutat. Res. 38, 33–42 (1976).

    Article  CAS  PubMed  Google Scholar 

  118. Wong, P. K. Mutagenicity of heavy metals. Bull. Environ. Contam. Toxicol. 40, 597–603 (1988).

    Article  CAS  PubMed  Google Scholar 

  119. Asakura, K. et al. Genotoxicity studies of heavy metals: lead, bismuth, indium, silver and antimony. J. Occup. Health 51, 498–512 (2009).

    Article  CAS  PubMed  Google Scholar 

  120. Rogers, H. J., Woods, V. E. & Synge, C. Antibacterial effect of the scandium and indium complexes of enterochelin on Escherichia coli. J. Gen. Microbiol. 128, 2389–2394 (1982).

    CAS  PubMed  Google Scholar 

  121. Olakanmi, O. et al. Gallium disrupts iron uptake by intracellular and extracellular Francisella strains and exhibits therapeutic efficacy in a murine pulmonary infection model. Antimicrob. Agents Chemother. 54, 244–253 (2010).

    Article  CAS  PubMed  Google Scholar 

  122. Malfertheiner, P. et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, Phase 3 trial. Lancet 377, 905–913 (2011).

    Article  CAS  PubMed  Google Scholar 

  123. Andrews, P. C. et al. Remarkable in vitro bactericidal activity of bismuth(III) sulfonates against Helicobacter pylori. Dalton Trans. 41, 11798–11806 (2012).

    Article  CAS  PubMed  Google Scholar 

  124. Stout, J. E. & Yu, V. L. Experiences of the first 16 hospitals using copper–silver ionization for Legionella control: implications for the evaluation of other disinfection modalities. Infect. Control Hosp. Epidemiol. 24, 563–568 (2003). The results of field testing suggesting that the use of Cu–Ag ionization systems can eliminate hospital outbreaks of Legionnaires' disease.

    Article  PubMed  Google Scholar 

  125. Rai, M., Yadav, A. & Gade, A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol. Adv. 27, 76–83 (2009).

    Article  CAS  PubMed  Google Scholar 

  126. Sharma, V. K., Yngard, R. A. & Lin, Y. Silver nanoparticles: green synthesis and their antimicrobial activities. Adv. Colloid Interface Sci. 145, 83–96 (2009).

    Article  CAS  PubMed  Google Scholar 

  127. Sondi, I. & Salopek-Sondi, B. Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. J. Colloid Interface Sci. 275, 177–182 (2004).

    Article  CAS  PubMed  Google Scholar 

  128. Stoimenov, P. K., Klinger, R. L., Marchin, G. L. & Klabunde, K. J. Metal oxide nanoparticles as bactericidal agents. Langmuir 18, 6679–6686 (2002).

    Article  CAS  Google Scholar 

  129. Ruparelia, J. P., Chatterjee, A. K., Duttagupta, S. P. & Mukherji, S. Strain specificity in antimicrobial activity of silver and copper nanoparticles. Acta Biomater. 4, 707–716 (2008).

    Article  CAS  PubMed  Google Scholar 

  130. Bandyopadhyay, S., Peralta-Videa, J. R., Plascencia-Villa, G., Jose-Yacaman, M. & Gardea-Torresdey, J. L. Comparative toxicity assessment of CeO2 and ZnO nanoparticles towards Sinorhizobium meliloti, a symbiotic alfalfa associated bacterium: use of advanced microscopic and spectroscopic techniques. J. Hazard. Mater. 241–242, 379–386 (2012).

  131. Luef, B. et al. Iron-reducing bacteria accumulate ferric oxyhydroxide nanoparticle aggregates that may support planktonic growth. ISME J. 7, 338–350 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Morones, J. R. et al. The bactericidal effect of silver nanoparticles. Nanotechnology 16, 2346–2353 (2005).

    Article  CAS  PubMed  Google Scholar 

  133. Pal, S., Tak, Y. K. & Song, J. M. Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the Gram-negative bacterium Escherichia coli. Appl. Environ. Microbiol. 73, 1712–1720 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. El Badawy, A. M. et al. Surface charge-dependent toxicity of silver nanoparticles. Environ. Sci. Technol. 45, 283–287 (2011).

    Article  CAS  PubMed  Google Scholar 

  135. Gunawan, C., Teoh, W. Y., Marquis, C. P. & Amal, R. Cytotoxic origin of copper(II) oxide nanoparticles: comparative studies with micron-sized particles, leachate, and metal salts. ACS Nano 5, 7214–7225 (2011).

    Article  CAS  PubMed  Google Scholar 

  136. Applerot, G. et al. Understanding the antibacterial mechanism of CuO nanoparticles: revealing the route of induced oxidative stress. Small 8, 3326–3337 (2012).

    Article  CAS  PubMed  Google Scholar 

  137. Sotiriou, G. A. & Pratsinis, S. E. Antibacterial activity of nanosilver ions and particles. Environ. Sci. Technol. 44, 5649–5654 (2010).

    Article  CAS  PubMed  Google Scholar 

  138. Xiu, Z. M., Zhang, Q. B., Puppala, H. L., Colvin, V. L. & Alvarez, P. J. Negligible particle-specific antibacterial activity of silver nanoparticles. Nano Lett. 12, 4271–4275 (2012). The demonstration that metal nanoparticles that cannot become ionized are non-toxic to bacteria.

    Article  CAS  PubMed  Google Scholar 

  139. Highsmith, J. Nanoparticles in biotechnology, drug development and drug delivery. Report No. BIO113A (BCC Research: Market Forecasting, 2012).

  140. Wilks, S. A., Michels, H. & Keevil, C. W. The survival of Escherichia coli O157 on a range of metal surfaces. Int. J. Food Microbiol. 105, 445–454 (2005).

    Article  CAS  PubMed  Google Scholar 

  141. Quaranta, D. et al. Mechanisms of contact-mediated killing of yeast cells on dry metallic copper surfaces. Appl. Environ. Microbiol. 77, 416–426 (2011).

    Article  CAS  PubMed  Google Scholar 

  142. Espirito Santo, C. et al. Bacterial killing by dry metallic copper surfaces. Appl. Environ. Microbiol. 77, 794–802 (2011).

    Article  CAS  PubMed  Google Scholar 

  143. Warnes, S. L., Highmore, C. J. & Keevil, C. W. Horizontal transfer of antibiotic resistance genes on abiotic touch surfaces: implications for public health. mBio 3, e00489–12 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Hoffman, L. R. & Ramsey, B. W. Cystic fibrosis therapeutics: the road ahead. Chest 143, 207–213 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Gans, J., Wolinsky, M. & Dunbar, J. Computational improvements reveal great bacterial diversity and high metal toxicity in soil. Science 309, 1387–1390 (2005).

    Article  CAS  PubMed  Google Scholar 

  146. Alexander, J. W. History of the medical use of silver. Surg. Infect. 10, 289–292 (2009).

    Article  Google Scholar 

  147. Borkow, G. & Gabbay, J. Copper, an ancient remedy returning to fight microbial, fungal and viral infections. Curr. Chem. Biol. 3, 272–278 (2009).

    CAS  Google Scholar 

  148. Ayres, P. G. Alexis Millardet: France's forgotten mycologist. Mycologist 18, 23–26 (2004).

    Article  Google Scholar 

  149. Dixon, B. Pushing Bordeaux mixture. Lancet Infect. Dis. 4, 594 (2004).

    Article  PubMed  Google Scholar 

  150. Sims, J. M. On the treatment of vesicovaginal fistula. Am. J. Med. Sci. 45, 59–82 (1852).

    Article  Google Scholar 

  151. Crede, C. S. F. Die verhütung der augenentzündung der neugeborenen. Arch. Gynakol. 17, 50–53 (1881) (in German).

    Article  Google Scholar 

  152. Silver, S., Phung le, T. & Silver, G. Silver as biocides in burn and wound dressings and bacterial resistance to silver compounds. J. Ind. Microbiol. Biotechnol. 33, 627–634 (2006).

    Article  CAS  PubMed  Google Scholar 

  153. Pereira, J. Materia medica, or pharmacology, and general therapeutics. Lond. Med. Gaz. 18, 305–314 (1836).

    Google Scholar 

  154. Frazer, A. D. & Edin, M. B. Tellurium in the treatment of syphillis. Lancet 216, 133–134 (1930).

    Article  Google Scholar 

  155. Keyes, E. L. The treatment of gonorrhea of the male urethra. JAMA 75, 1325–1329 (1920).

    Article  Google Scholar 

  156. Hodges, N. D. C. The value of mercuric chloride as a disinfectant. Science 13, 62–64 (1889).

    Google Scholar 

  157. Ehrlich, P. & Bertheim, A. Über das salzsaure 3.3′-Diamino-4.4′ -dioxy-arsenobenzol und seine nächsten Verwandten. Ber. Dtsch. Chem. Ges. 45, 756–766 (1912) (in German).

    Article  CAS  Google Scholar 

  158. Changela, A. et al. Molecular basis of metal-ion selectivity and zeptomolar sensitivity by CueR. Science 301, 1383–1387 (2003).

    Article  CAS  PubMed  Google Scholar 

  159. Silver, S. & Phung, L. T. Bacterial heavy metal resistance: new surprises. Annu. Rev. Microbiol. 50, 753–789 (1996).

    Article  CAS  PubMed  Google Scholar 

  160. Dimkpa, C. O. et al. Involvement of siderophores in the reduction of metal-induced inhibition of auxin synthesis in Streptomyces spp. Chemosphere 74, 19–25 (2008).

    Article  CAS  PubMed  Google Scholar 

  161. Chaturvedi, K. S., Hung, C. S., Crowley, J. R., Stapleton, A. E. & Henderson, J. P. The siderophore yersiniabactin binds copper to protect pathogens during infection. Nature Chem. Biol. 8, 731–736 (2012).

    Article  CAS  Google Scholar 

  162. Johnston, C. W. et al. Gold biomineralization by a metallophore from a gold-associated microbe. Nature Chem. Biol. 9, 241–243 (2013).

    Article  CAS  Google Scholar 

  163. Mullen, M. D. et al. Bacterial sorption of heavy metals. Appl. Environ. Microbiol. 55, 3143–3149 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Langley, S. & Beveridge, T. J. Effect of O-side-chain-lipopolysaccharide chemistry on metal binding. Appl. Environ. Microbiol. 65, 489–498 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Zannoni, D., Borsetti, F., Harrison, J. J. & Turner, R. J. The bacterial response to the chalcogen metalloids Se and Te. Adv. Microb. Physiol. 53, 1–71 (2008).

    CAS  PubMed  Google Scholar 

  166. Carrondo, M. A. Ferritins, iron uptake and storage from the bacterioferritin viewpoint. EMBO J. 22, 1959–1968 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Lemire, J., Mailloux, R., Auger, C., Whalen, D. & Appanna, V. D. Pseudomonas fluorescens orchestrates a fine metabolic-balancing act to counter aluminum toxicity. Environ. Microbiol. 12, 1384–1390 (2010).

    CAS  PubMed  Google Scholar 

  168. Zhou, Y., Kong, Y., Kundu, S., Cirillo, J. D. & Liang, H. Antibacterial activities of gold and silver nanoparticles against Escherichia coli and bacillus Calmette-Guérin. J. Nanobiotechnology 10, 19 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Yu, D. & Yam, V. W. Hydrothermal-induced assembly of colloidal silver spheres into various nanoparticles on the basis of HTAB-modified silver mirror reaction. J. Phys. Chem. B 109, 5497–5503 (2005).

    Article  CAS  PubMed  Google Scholar 

  170. Sun, Y. & Xia, Y. Shape-controlled synthesis of gold and silver nanoparticles. Science 298, 2176–2179 (2002).

    Article  CAS  PubMed  Google Scholar 

  171. Saier, M. H. Jr. A functional-phylogenetic classification system for transmembrane solute transporters. Microbiol. Mol. Biol. Rev. 64, 354–411 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

J.A.L. is supported by a postdoctoral fellowship from the Natural Sciences and Engineering Research Council (NSERC) of Canada. J.J.H. is supported by a fellowship from the Canadian Institute for Health Research (CIHR). Research in the laboratory of R.J.T. is supported by a Discovery Grant from the NSERC and an Operating Grant from the CIHR.

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Supplementary Table 1

Examples of consumer products that contain an antimicrobial metal as an active ingredient (PDF 81 kb)

Glossary

Essential metals

Metals that are required for the normal physiology and function of organisms; these include Na, Mg, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se and Mo. Thus far, Cd has been found to be essential for the function of only one enzyme in a few bacterial species

Non-essential metals

Metals that have no known biological function for an organism.

Chelates

Chemical compounds in which a heterocyclic ring has been formed through the coordinate bonding of a metal atom to at least two non-metal atoms.

Nanomaterials

Materials containing particles with an external dimension in the size range of 1–100 nm. At the nanoscale (10−9 m) range, materials can have novel mechanical, electromagnetic and chemical properties that distinguish them from the same material in bulk.

Biocides

Chemical agents that are capable of destroying a living organism.

Transition metals

Elements that either have an incomplete d sub-shell of electrons or can give rise to cations with an incomplete d sub-shell. These include all elements in groups 3–12 of the periodic table, with the exception of the lanthanides and actinides.

Other metals

Any of the metallic elements within groups 13–15 of the periodic table.

Metalloids

Chemical elements with properties that resemble those of both metals and non-metals; these elements include B, Si, Ge, As, At, Te and Po.

Hyperosmotic shock

A sudden increase in the solute concentration surrounding a cell, resulting in water leakage from the cell through osmosis. This activity disrupts normal transport and metabolic processes.

Donor atom selectivity

The principle that, within a mixture of various ligands and metals, differences in affinity will result in the formation of specific types and quantities of coordination complexes.

Speciation

The distinct chemical forms, compounds and concentrations in which an element occurs in its milieu.

Coordination chemistry

The science concerned with the interactions of organic and inorganic ligands with a central metal atom.

Ligand field theory

An application of molecular orbital theory that describes the bonding and orbital arrangements of transition metals in coordination complexes.

Ionic mimicry

In the context of this Review, the ability of an unbound, cationic metal species to imitate an essential element or cationic form of that element.

Molecular mimicry

In the context of this Review, the phenomenon whereby a complex formed between a metal species and a ligand serves as a structural or functional homologue of another endogenous biomolecule.

Hard–soft acid base theory

An empirically derived chemical theory that helps us to understand the factors that drive reactions in complex mixtures of inorganic and organic reactants.

Standard electrode potentials

The reduction potential of a half-reaction (in Volts) relative to the standard hydrogen electrode at precisely defined conditions (25 °C, 1 atm and a 1 M concentration for each aqueous species).

Valence electrons

The electrons of an atom that participate in the formation of chemical bonds.

Oxyanion

An anionic compound in which any element is bonded to O.

Electron paramagnetic resonance

(EPR). A spectroscopic technique for studying materials with unpaired electrons.

Reactive oxygen species

(ROS). Highly reactive, cytotoxic molecules formed by the incomplete, one-electron reduction of O. ROS include the superoxide anion (O2•−), peroxides (such as H2O2), the hydroxyl radical (OH) and hypochlorite (HOCl).

Metal-catalysed oxidation

A free radical-generating system in which a Fenton-active metal catalyses the oxidative modification of a biomolecule.

Autoxidation

The thermodynamically favourable oxidation of a reduced compound by O2. Certain metals can behave as catalysts to increase the rate of this reaction.

Free radical

Any atomic or molecular species that is capable of independent existence and contains one or more unpaired electrons. According to this definition, many transition metal ions are considered free radicals.

Glutathione

A tripeptide antioxidant (Glu-Cys-Gly) in which a γ-peptide bond joins the primary amine group of cysteine to the carboxyl group of the glutamate side chain. Equilibrium between reduced glutathione (GSH) and oxidized glutathione (GSSG) helps to maintain the cellular redox state of many bacterial species.

Diffusion-controlled rate

A chemical reaction rate so rapid that it is restricted only by the diffusion rates of the reactants in solution.

Lewis acid

An electron-pair acceptor that is able to react with a Lewis base to form an adduct by sharing an electron pair provided by the Lewis base.

δ-aminolevulinic acid dehydratase

(ALAD). An evolutionarily conserved enzyme that catalyses the production of porphobilinogen, a key precursor in the haem biosynthesis pathway.

Chemiosmotic potential

The motive force generated by a transmembrane Na+ or proton gradient.

Thiobarturic acid-reactive substances

(TBARS). By-products of lipid peroxidation, such as malondialdehyde, that can react with thiobarbituric acid to produce fluorescent adducts. These adducts are used to indirectly detect and quantify fatty acid peroxidation.

S-sparing response

A physiological adaptation in yeast that modifies the proteome by reducing the abundance of S-rich proteins.

Ames test

A microbiological assay that is used to assess the mutagenic potential of chemical compounds.

Colloids

Particulates of a substance that are evenly distributed (and thus known as the dispersed phase) throughout a dispersion medium (known as the continuous phase).

Zeolite

A microporous aluminosilicate mineral that can adsorb water and ions.

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Lemire, J., Harrison, J. & Turner, R. Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 11, 371–384 (2013). https://doi.org/10.1038/nrmicro3028

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