Skip to main content
SpringerLink
Log in

Understanding cellular responses to toxic agents: a model for mechanism-choice in bacterial metal resistance

  • Published:
Journal of Industrial Microbiology

Summary

Bacterial resistances to metals are heterogeneous in both their genetic and biochemical bases. Metal resistance may be chromosomally-, plasmid- or transposonencoded, and one or more genes may be involved; at the biochemical level at least six different mechanisms are responsible for resistance. Various types of resistance mechanisms can occur singly or in combination and for a particular metal different mechanisms of resistance can occur in the same species. To understand better the diverse responses of bacteria to metal ion challenge we have constructed a qualitative model for the selection of metal resistance in bacteria. How a bacterium becomes resistant to a particular metal depends on the number and location of cellular components sensitive to the specific metal ion. Other important selective factors include the nature of the uptake systems for the metal, the role and interactions of the metal in the normal metabolism of the cell and the availability of plasmid (or transposon) encoded resistance mechanisms. The selection model presented is based on the interaction of these factors and allows predictions to be made about the evolution of metal resistance in bacterial populations. It also allows prediction of the genetic basis and of mechanisms of resistance which are in substantial agreement with those in well-documented populations. The interaction of, and selection for resistance to, toxic substances in addition to metals, such as antibiotics and toxic analogues, involve similar principles to those concerning metals. Potentially, models for selection of resistance to any substance can be derived using this approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Amyes, S.G.B. and C.G. Gemmell. 1992. Antibiotic resistance in bacteria. J. Med. Microbiol. 36: 4–29.

    PubMed  Google Scholar 

  2. Anderson, O.S. 1978. Permeability properties of unmodified lipid bilayer membranes. In: Membrane Transport in Biology (G. Giebisch, D.C. Tosteson and H.H. Ussing, eds), pp. 369–446. Springer Verlag, Berlin.

    Google Scholar 

  3. Aruoma, O.I. and H. Halliwell. 1991. DNA damage and free radicals. Chem. Brit. 149–152.

  4. Babich, H. and G. Stotzky. 1980. Environmental factors that influence the toxicity of heavy metal and gaseous pollutants to microorganisms. Crit. Rev. Microbiol. 9: 99–145.

    Google Scholar 

  5. Bagg, A. and J.B Neilands. 1987. Molecular mechanism of regulation of siderophore-mediated iron assimilation. Microbiol. Rev. 51: 509–518.

    PubMed  Google Scholar 

  6. Beswick, P.H., G.H. Hall, A.J. Hook, K. Little, D. McBrien and K.A.K. Lott. 1976. Copper toxicity: evidence for the conversion of cupric to cuprous cooperin vivo under anaerobic conditions. Chem.-Biol. Interactions 14: 347–356.

    Google Scholar 

  7. Beyersmann, D. 1994. Interactions in metal carcinogenicity. Toxicol. L Lett. 121: 141–146.

    Google Scholar 

  8. Bitton, G. and V. Freihofer. 1978. Influence of extracellular polysaccharides on the toxicity of copper and cadmium towardsKlebsiella aerogenes. Microbial Ecol. 4: 119–125.

    Google Scholar 

  9. Brown, N.L., J. Camakaris, B.T.O. Lee, T. Williams, A.P. Morby, J. Parkhill and D.A. Rouch. 1991. Bacterial resistances to mercury and copper. J. Cell. Biochem. 46: 106–114.

    PubMed  Google Scholar 

  10. Bryson, J.W., T.V. O'Halloran, D.A. Rouch, N.L. Brown, J. Camakaris and B.T.O. Lee. 1993. Chemical and genetic studies of copper resistance inE. coli. In: Bioinorganic Chemistry (K.D. Karlin and Z. Tyeklár, eds), pp. 101–109, Chapman and Hall, New York.

    Google Scholar 

  11. Chopra, I. 1975. Mechanism of plasmid mediated resistance to cadmium inStaphylococcus aureus. Antimicrob. Agents Chemother. 7: 8–14.

    PubMed  Google Scholar 

  12. Cooksey, D.A. 1994. Molecular mechanisms of copper resistance and accumulation in bacteria. FEMS Microbiol. Rev. 14: 381–386.

    PubMed  Google Scholar 

  13. Davey, R.B. and D.C. Reanney. 1980. Extrachromosomal genetic elements and the adaptive evolution of bacteria. Evol. Biol. 13: 113–147.

    Google Scholar 

  14. Fraústo da Silva, J.J.R. and R.J.P. Williams. 1993. The Biological Chemistry of the Elements. Oxford University Press, Oxford.

    Google Scholar 

  15. Freedman, J.H., M.R. Cirolo and J. Peisach. 1989. The role of glutathione in copper metabolism and toxicity. J. Biol. Chem. 264: 5598–5605.

    PubMed  Google Scholar 

  16. Gadd, G.M. and A.J. Griffiths. 1978. Microorganisms and heavy metal toxicity. Microbial Ecol. 4: 303–317.

    Google Scholar 

  17. Gupta, A., A.P. Morby, J.S. Turner, B.A. Whitton and N.J., Robinson. 1993. Deletion within the metallothionein locus of cadmiumtolerantSynchecococcus PCC 6301 involving a highly iterated palindrome (HIP1). Mol. Microbiol. 7: 189–195.

    PubMed  Google Scholar 

  18. Gupta A., B.A. Whitton, A.P. Morby, J.W. Huckle and N.J. Robinson. 1992. Amplification and rearrangement of a prokaryotic metallothionein locus,smt inSynechococcus PCC 6301 selected for tolerance to cadmium. Proc. Roy. Soc. B 248: 273–281.

    Google Scholar 

  19. Gutteridge, J.M.C. and B. Halliwell. 1990. The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem. Sci. 15: 129–135.

    PubMed  Google Scholar 

  20. Hangstein, W.G. 1976. Uncoupling of oxidative phosphorylation. Biochim. Biophys. Acta 456: 129–148.

    PubMed  Google Scholar 

  21. Hao, O.J. and C.H. Chang. 1988. Metal toxicity on phosphate removal in pure culture and in activated sludge systems. J. Environ. Engineer. 114: 38–53.

    Google Scholar 

  22. Hughes, M.N. and R.K. Poole. 1989. Metals and Micro-organisms. Chapman and Hall, London.

    Google Scholar 

  23. Hughes, M.N. and R.K. Poole. 1991. Metal speciation and microbial growth—the hard (and soft) facts. J. Gen. Microbiol. 137: 725–734.

    Google Scholar 

  24. Ichikawa, H., K. Ronowicz, M. Hicks and J.M. Gebicki. 1987. Lipid peroxidation is not the cause of lysis of human erythrocytes exposed to inorganic or methyl mercury. Arch. Biochem. Biophys. 259: 46–51.

    PubMed  Google Scholar 

  25. Ivey, D.M., A.A. Guffanti, Z.H. Shen, N. Kudyan and T.A. Krulwich. 1992. TheCadC gene-product of alkaliphilicBacillus firmus OF4 partially restores Na+ resistance to anEscherichia coli strain lacking an Na+/H+ antiporter (NhaA). J. Bacteriol. 174: 4878–4884.

    PubMed  Google Scholar 

  26. Jocelyn, P.C. 1972. Biochemistry of the SH Group. Academic Press, London.

    Google Scholar 

  27. Jungmann, J., H.-A. Reins, C. Schobert and S. Jentsch. 1993. Resistance to cadmium mediated by ubiquitin-dependent proteolysis. Nature 361: 369–371.

    PubMed  Google Scholar 

  28. Khesin, R.B. and E.V. Karasyova. 1984. Mercury-resistant plasmids in bacteria from a mercury and antimony deposit area. Molec. Gen. Genet. 197: 280–285.

    PubMed  Google Scholar 

  29. Kronmann, M.J. and S.C. Bratcher. 1984. Conformational changes induced by zinc and terbium binding to native bovine α-lactalbumin and calcium free α-lactalbumin. J. Biol. Chem. 259: 10887–10895.

    PubMed  Google Scholar 

  30. Lee, B.T.O., S. Rogers, A. Bergemann, J. Camakaris and D.A. Rouch. 1990. Bacterial response to copper in the environment: copper resistance inEscherichia coli as a model system. In: Metal Speciation in the Environment (J.A.C. Broekaert, S. Güçer and F. Adams, eds), pp. 625–632. Springer-Verlag, Berlin.

    Google Scholar 

  31. Lloyd-Jones, G., A.M. Osborn, D.A. Ritchie, P. Strike, J.L. Hobman, N.L. Brown and D.A. Rouch. 1994. Accumulation and intracellular fate of tellurite in tellurite-resistantEscherichia coli: a model for the mechanism of resistance. FEMS Microbiol. Lett. 118: 113–120.

    PubMed  Google Scholar 

  32. Lloyd-Jones, G., D.A. Ritchie and P. Strike. 1991. Biochemical and biophysical analysis of plasmid pMJ600-encoded tellurite [TeO3 2−] resistance. FEMS Microbiol. Lett. 81: 19–24.

    Google Scholar 

  33. Lutkenhaus, J.F. 1977. Role of a major outer membrane protein inEscherichia coli. J. Bacteriol. 131: 631–637.

    PubMed  Google Scholar 

  34. Macaskie, L.E., K.M. Bonthrone and D.A. Rouch. 1994. Phosphatase-mediated heavy metal accumulation by aCitrobacter sp. and related enterobacteria. FEMS Microbiol. Lett. 121: 141–146.

    PubMed  Google Scholar 

  35. Macdonald, T.L. and R.B. Martin. 1988. Aluminium ion in biological systems. Trends Biochem. Sci. 13: 15–19.

    PubMed  Google Scholar 

  36. Marzilli, L.G., T.J. Kistenmacher and G.L. Eichhorn. 1980. Structural principles of metal ion-nucleotide and metal ion-nucleic acid interactions. In: Nucleic Acid-metal Ion Interaction (T.G. Spiro, ed.), pp. 179–250. J. Wiley and Sons, New York.

    Google Scholar 

  37. Mitra, R.S. and I.A. Bernstein. 1978. Single strand breakage in DNA ofE. coli exposed to Cd2+. J. Bacteriol. 121: 1180–1188.

    Google Scholar 

  38. Moore, S.A., D.M.C. Moennich and M.J. Gresser. 1983. Synthesis and hydrolysis of ADP-arsenate by beef heart submitochondrial particles. J. Biol. Chem. 258: 6266–6271.

    PubMed  Google Scholar 

  39. Nieboer, E. and D.H.S. Richardson. 1980. The replacement of the nondescript term “heavy metals” by a biologically and chemically significant classification of metal ions. Environ. Pollut. (Ser. B) 1: 3–26.

    Google Scholar 

  40. Nikaido, H. and M. Vaara. 1985. Molecular basis of bacterial outer membrane permeability. Microbiol. Rev. 49: 1–32.

    PubMed  Google Scholar 

  41. Nucifora, G., L. Chu, T.K. Misra and S. Silver. 1989. Cadmium resistance fromStaphylococcus aureus plasmid pI258cadA gene results from a cadmium-efflux ATPase. Proc. Natl Acad. Sci. USA 86: 3544–3548.

    PubMed  Google Scholar 

  42. Pan, T. and O.C. Uhlenbeck. 1992. In vitro selection of RNAs that undergo autolytic cleavage with Pb2+. Biochemistry 31: 3887–3895.

    PubMed  Google Scholar 

  43. Pan-Hou, H.S.K. and N. Imura. 1981. Role of hydrogen sulfide in mercury resistance determined by plasmid ofClostridium cochlearium T-2. Arch. Microbiol. 129: 49–52.

    PubMed  Google Scholar 

  44. Passow, H. and A. Rothstein. 1960. The binding of mercury by the yeast cell in relation to change in permeability. J. Gen. Physiol. 43: 621–633.

    PubMed  Google Scholar 

  45. Pickett, A.W., I.S. Carter and A.C.R. Dean. 1976. Enzymic activities of cadmium and zinc tolerant strains ofKlebsiella aerogenes grown in glucose limited chemostats. Microbios 15: 105–111.

    PubMed  Google Scholar 

  46. Rehder, D. 1992. Structure and function of vanadium compounds in living organisms. Biometals 5: 3–12.

    PubMed  Google Scholar 

  47. Robinson, N.J., A. Gupta, A.P. Fordham-Skelton, R.R.D. Croy, B.A. Whitton and J.W. Huckle. 1990. Prokaryotic metallothionein gene characterization and expression: chromosome crawling by ligation-mediated PCR. Proc. Roy. Soc. Lond. B 242: 241–247.

    Google Scholar 

  48. Rouch, D.A. 1986. Plasmid-mediated copper resistance inE. coli. PhD thesis, University of Melbourne.

  49. Rouch, D.A., J. Camakaris and B.T.O. Lee. 1989. Copper transport inEscherichia coli. In: Metal Ion Homeostasis: Molecular Biology and Chemistry (D.H. Hamer and D.R. Winge, eds), pp. 469–477, Alan R. Liss, New York.

    Google Scholar 

  50. Rouch, D.A., J. Parkhill and N.L. Brown. 1994. Induction of bacterial mercury- and copper-responsive promoters: functional differences between inducible systems and for their use in genefusions forin vivo biosensors. J. Ind. Microbiol. 14: in press.

  51. Schreurs, W.J. and H. Rosenberg. 1982. Effect of silver ions on transport and retention of phosphate byEscherichia coli. J. Bacteriol. 152: 7–13.

    PubMed  Google Scholar 

  52. Silver, S.. 1978. Transport of cations and anions. In: Bacterial Transport (B.P. Rosen, ed.), pp. 221–324, Marcel Dekker, New York.

    Google Scholar 

  53. Silver, S., G. Ji, S. Broer, S. Dey, D. Dou and B.P. Rosen. 1993. Orphan enzyme or patriarch of a new tribe: the arsenic resistance ATPase of bacterial plasmids. Mol. Microbiol. 8: 637–642.

    PubMed  Google Scholar 

  54. Silver, S., J. Schottel and A. Weiss. 1975. Bacterial resistance to toxic metals determined by extrachromosomal R factors. Proceedings 3rd International Biodegradation Symposium, Kingston, Rhode Is., USA.

  55. Silver, S. and W. Walderhaug. 1992. Gene regulation of plasmid-determined and chromosome-determined inorganic ion transport in bacteria. Microbiol. Rev. 56: 195–228.

    PubMed  Google Scholar 

  56. Slawson, R.M., M.I. Van Dyke, H. Lee and J.T. Trevors. 1992. Germanium and silver resistance, accumulation, and toxicity in microorganisms. Plasmid 27: 72–79.

    PubMed  Google Scholar 

  57. Steinmann, H.M. 1992. Construction of anEscherichia coli K-12 strain deleted for manganese and iron superoxide dismutate genes and its use in cloning the iron superoxide dismutase gene ofLegionella pneumophila. Mol. Gen. Genet. 232: 427–430.

    PubMed  Google Scholar 

  58. Turner, J.S., A.P. Morby, B.A. Whitton, A. Gupta and N.J. Robinson. 1993. Construction of Zn2+/Cd2+ hypersensitive cyanobacterial mutants lacking a functional metallothionein locus. J. Biol. Chem. 268: 4494–4498.

    PubMed  Google Scholar 

  59. Vallee, B.L. and D.D. Ulmer. 1972. Biochemical effects of mercury, cadmium, and lead. Ann. Rev. Biochem. 41: 91–128.

    PubMed  Google Scholar 

  60. Walter, E.G. and D.E. Taylor. 1992. Plasmid-mediated resistance to tellurite: expressed and cryptic. Plasmid 27: 52–64.

    PubMed  Google Scholar 

  61. Williams, R.J.P. 1984. Structural aspects of metal toxicity. In: Changing Metal Cycles and Human Health (J.O. Nriagu, ed.), pp. 251–263. Springer-Verlag, Berlin.

    Google Scholar 

  62. Willsky, G.R. and M.H. Malamy. 1980. Effect of arsenate on inorganic phosphate transport inEscherichia coli. J. Bacteriol. 144: 366–374.

    PubMed  Google Scholar 

  63. Yamane, T. and N. Davidson. 1962. On the complexing of deoxyribonucleic acid by silver(I). Biochim. Biophys. Acta 55: 609–621.

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Duncan A. Rouch

    Present address: New Chemistry Laboratory, University of Oxford, OX1 3QT, Oxford, UK

Authors and Affiliations

  1. School of Biological Sciences, The University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK

    Duncan A. Rouch & Andy P. Morby

  2. Department of Genetics, University of Melbourne, 3052, Parkville, Victoria, Australia

    Barry T. O. Lee

Authors
  1. Duncan A. Rouch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barry T. O. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andy P. Morby
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rouch, D.A., Lee, B.T.O. & Morby, A.P. Understanding cellular responses to toxic agents: a model for mechanism-choice in bacterial metal resistance. Journal of Industrial Microbiology 14, 132–141 (1995). https://doi.org/10.1007/BF01569895

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01569895

Key words

Search

Navigation