1. bookVolume 56 (2017): Issue 2 (January 2017)
Journal Details
First Published
01 Mar 1961
Publication timeframe
4 times per year
English, Polish
access type Open Access

Bacterial metallothioneins

Published Online: 21 May 2019
Volume & Issue: Volume 56 (2017) - Issue 2 (January 2017)
Page range: 171 - 179
Received: 01 Aug 2016
Accepted: 01 Nov 2016
Journal Details
First Published
01 Mar 1961
Publication timeframe
4 times per year
English, Polish

Heavy metals are found in all living organisms where, as indispensable microelements (e.g. zinc, iron, copper), are involved in endless metabolic processes. However, living organisms are also at a risk of exposure to highly toxic metals, including cadmium or lead, which do not play any physiological role. Among multiple mechanisms associated with the maintenance of micronutrient homeostasis and detoxification of unwanted metals, there is a family of low-molecular-weight, cysteine-rich proteins, able to chelate multiple metal ions i.e. the metallothioneins (MTs). They are widely distributed among Eucaryota, however, they have also been found in some limited Procaryota, including cyanobacteria, pseudomonads and mycobacteria. These bacterial MTs differ in terms of primary structure, the number and type of metal ions they bind, as well as with regard to their physiological functions. The expression of bacterial MTs is regulated by metals via metalosensors. MTs from cyanobacteria seem to be involved in zinc homeostasis, while in Pseudomonas they are linked to cadmium detoxification. In Mycobacterium, MTs bind copper ions and may play a pivotal role in the virulence of these bacteria. The presence of MTs in other groups of bacteria remains questionable. Problems with identification of new bacterial MTs are mainly associated with low level of homology between MT amino acid sequences of different bacterial groups. Further research is needed to evaluate the physiological functions of metallothioneins in Procaryota.

1. Introduction. 2. The history of discoveries of bacterial metallothioneins. 3. Structure and metal-binding properties of bacterial MTs. 4. Functions of bacterial metallothioneins. 5. Regulation of metallothionein gene expression. 6. Presence of metallothioneins in bacteria. 7. Summary

1. Wstęp. 2. Historia odkryć metalotionein u bakterii. 3. Budowa i sposób wiązania jonów metali ciężkich przez bakteryjne MT. 4. Funkcje metalotionein bakteryjnych. 5. Regulacja ekspresji bakteryjnych metalotionein. 6. Obecność metalotionein u bakterii. 7. Podsumowanie

Key words

Słowa kluczowe

Binz P.A., Kägi J.H.R.: Metallothionein: molecular evolution and classification (w) Metallothionein IV, red. Klaassen C.D. Springer, Basel 1999, s. 7–1310.1007/978-3-0348-8847-9_2Search in Google Scholar

Bruins M.R., Kapil S., Oehme F.W.: Microbial resistance to metals in the environment. Ecotoxicol. Environ. Saf. 45, 198–207 (2000)Search in Google Scholar

Blindauer C.A., Harrison M.D., Parkinson J.A., Robinson A.K., Cavet J.S., Robinson N.J., Sadler P.J.: A metallothionein containing a zinc finger within a four-metal cluster protects a bacterium from zinc toxicity. Proc. Natl. Acad. Sci. USA, 98, 9593–9598 (2001)10.1073/pnas.171120098Search in Google Scholar

Blindauer C.A., Harrison M.D., Robinson A.K., Parkinson J.A., Bowness P.W., Sadler P.J., Robinson N.J.: Multiple bacteria encode metallothioneins and SmtA-like zinc fingers. Mol. Microbiol. 45, 1421–1432 (2002)Search in Google Scholar

Blindauer C.A., Sadler P.J.: How to hide zinc in a small protein. Acc. Chem. Res. 38, 62–69 (2005)Search in Google Scholar

Blindauer C.A.: Bacterial metallothioneins (w) Metallothioneins and related chelators. Metal ions in life science vol. 5, red. Sigel A., Sigel H., Sigiel R.K.O. Royal Society of Chemistry, Cambridge 2009, s. 51–8110.1039/9781847559531-00051Search in Google Scholar

Blindauer C.A.: Bacterial metallothioneins: past, present, and questions for the future. J. Biol. Inorg. Chem. 16, 1011–1024 (2011)Search in Google Scholar

Busenlehner L.S., Pennella M.A., Giedroc D.P.: The SmtB/ArsR family of metalloregulatory transcriptional repressors: structural insights into prokaryotic metal resistance. FEMS Microbiol. Rev. 27, 131–143 (2003)10.1016/S0168-6445(03)00054-8Search in Google Scholar

Capdevila M., Atrian S.: Metallothionein protein evolution: a miniassay. J. Biol. Inorg. Chem. 16, 977–989 (2011)Search in Google Scholar

Capdevila M., Bofill R., Palacios Ò., Atrian S.: State-of-art of metallothioneins at the beginning of the 21st century. Coord. Chem. Rev. 256, 46–62 (2012)Search in Google Scholar

Cavet J.S., Meng W., Pennella M.A., Appelhoff R.J., Giedroc D.P., Robinson N.J.: A nickel-cobalt sensing ArsR-SmtB family repressor: contributions of cytosol and effector binding sites to metal selectivity. J. Biol. Chem. 277, 38441–38448 (2002)Search in Google Scholar

Clemens S.: Toxic metal accumulation, responses to exposure and mechanisms of tolerance in plants. Biochimie, 88, 1707–1719 (2006)10.1016/j.biochi.2006.07.00316914250Search in Google Scholar

Dąbrowska G., Mierek-Adamska A., Goc A.: Characteristics of Brassica napus L. metallothionein genes: expression in organs and during seed germination. Austr. J. Crops Sci. 7, 1324–1332 (2013)Search in Google Scholar

Daniels M.J., Turner-Cavet J.S., Selkirk R., Sun H., Parkinson J.A., Sadler P.J., Robinson N.J.: Coordination of Zn2+ (and Cd2+) by prokaryotic metallothionein. Involvement of Hisimidazole. J. Biol. Chem. 273, 22957–22961 (1998)Search in Google Scholar

Darwin K.H.: Mycobaterium tuberculosis and copper: a newly appreciated defense against an old foe? J. Biol. Chem. 290, 18962–18966 (2015)Search in Google Scholar

Enshaei M., Khanafari A., Sepahey A.A.: Metallothionein induction in two species of Pseudomonas exposed to cadmium and copper contamination. Iran J. Environ. Health Sci. Eng. 7, 287–298 (2010)Search in Google Scholar

Erbe J.L., Taylor K.B., Hall L.M.: Metalloregulation of the cyanobacterial smt locus: identification of SmtB binding sites and direct interaction with metals. Nucl. Acids Res. 23, 2472–2478 (1995)10.1093/nar/23.13.24723070537630724Search in Google Scholar

Festa R.A., Jones M.B., Butler-Wu S., Sinsimer D., Gerads R., Bishai W.R., Peterson S.N., Darwin K.H.: A novel copper-responsive regulon in Mycobacterium tuberculosis. Mol. Microbiol. 79, 133–148 (2011)Search in Google Scholar

Foster A.W., Robinson N.J.: Promiscuity and preferences of metallothioneins: the cell rules. BMC Biol. 9, 25–28 (2011)10.1186/1741-7007-9-25308417821527046Search in Google Scholar

Freisinger E.: Plant MTs – long neglected members of the metallothionein superfamily. Dalton Trans. 47, 6663–6675 (2008)10.1039/b809789e19153613Search in Google Scholar

Godt J., Scheidig F., Grosse-Siestrup C., Esche V., Brandenburg P., Reich A., Gronberg D.A.: The toxicity of cadmium and resulting hazards for human health. J. Occup. Med. Toxicol. 1, 22 (2006)10.1186/1745-6673-1-22157857316961932Search in Google Scholar

Gold B., Deng H., Bryk R., Vargas D., Eliezer D., Roberts J., Jiang X., Nathan C.: Identification of a copper-binding metallothionein in pathogenic mycobacterial. Nat. Chem. Biol. 4, 609–616 (2008)Search in Google Scholar

Gupta A., Whitton B.A., Morby A.P., Huckle J.W., Robinson N.J.: Amplification and rearrangement of a prokaryotic metallothionein locus smt in Synechococcus PCC 6301 selected for tolerance to cadmium. Proc. Biol. Sci. 248, 273–281 (1992)Search in Google Scholar

Hänsch R., Mendel R.R.: Physiological functions of mineral micronutrients (Cu, Zn, Mn, Fe, Ni, Mo, B, Cl). Curr. Opin. Plant Biol. 12, 259–266 (2009)Search in Google Scholar

Higham D.R, Sadler PJ., Scawen M.D.: Cadmium-resistant Pseudomonas putida synthesizes novel cadmium proteins. Science, 225, 1043–1046 (1984)10.1126/science.225.4666.104317783048Search in Google Scholar

Higham D.P., Sadler P.J., Scawen M.D.: Cadmium-binding proteins in Pseudomonas putida: pseudothioneins. Environ. Health Persp. 65, 5–11 (1986)Search in Google Scholar

Higgins K.A., Giedroc D.: Insights into protein allostery in the CsoR/RcnR family of transcriptional repressors. Chem. Lett. 43, 20–25 (2014)Search in Google Scholar

Huckle J.W., Morby A.P., Turner J.S., Robinson N.J.: Isolation of a prokaryotic metallothionein locus and analysis of transcriptional control by trace metal ions. Mol. Microbiol. 7, 177–187 (1993)Search in Google Scholar

Koszucka A.M., Dąbrowska G.: Roślinne metalotioneiny. Post. Biol. Kom. 33, 285–302 (2006)Search in Google Scholar

Kuroda M., Hayashi H., Ohta T.: Chromosome-determined zinc-responsible operon czr in Staphylococcus aureus strain 912. Microbiol. Immunol. 43, 115–125 (1999)Search in Google Scholar

Lane B., Kajoika R., Kennedy R.: The wheat-germ Ec protein is a zinc-containing metallothionein. Biochem. Cell Biol. 65, 1001–1005 (1987)Search in Google Scholar

Lane T.W., Saito M.A., George G.N., Pickering I.J, Prince R.C., Morel F.M.M.: A cadmium enzyme from a marine diatom. Nature, 435, 42 (2005)10.1038/435042aSearch in Google Scholar

Leszczyszyn O.I., White C.R.J., Blindauer C.A.: The isolated Cys2His2 site in Ec metallothionein mediates metal-specific protein folding. Mol. Bio. Syst. 6, 1592–1603 (2010)Search in Google Scholar

Leszczyszyn O.I., Imam H.T., Blindauer C.A.: Diversity and distribution of plant metallothioneins: a review of structure, properties and functions. Metallomics, 5, 1146–1169 (2013)10.1039/c3mt00072aSearch in Google Scholar

Liu T., Nakashima S., Hirose K., Shibasaka M., Katsuhara M., Ezaki B., Giedroc P.D., Kasamo K.: A novel cyanobacterial SmtB/ArsR family repressor regulates the expression of a CPX-ATPase and a metallothionein in response to both Cu(I)/Ag(I) and Zn(II)/Cd(II). J. Biol. Chem. 279, 17810–17818 (2004)Search in Google Scholar

Liu T., Nakashima S., Hirose K., Uemura Y., Shibasaka M., Katsuhara M., Kasamo K.: A metallothionein and CPx-ATPase handle heavy-metal tolerance in the filamentous cyanobacterium Oscillatoria brevis. FEBS Lett. 542, 159–163 (2003)10.1016/S0014-5793(03)00370-3Search in Google Scholar

Ma Z., Jacobsen F.E., Giedroc D.P.: Metal transporters and metal sensors: how coordination chemistry controls bacterial metal homeostasis. Chem. Rev. 109, 4644–4681 (2009)Search in Google Scholar

Maret W., Sandstead H.: Zinc requirements and the risks and benefits of zinc supplementation. J. Trace Elem. Med. Biol. 20, 3–20 (2005)Search in Google Scholar

Margoshes M., Vallee B.L.: A cadmium protein from equine kidney cortex. J. Am. Chem. Soc. 79, 4813–4814 (1957)Search in Google Scholar

Morby A.P., Turner J.S., Huckle J.W., Robinson N.J.: SmtB is a metal-dependent repressor of the cyanobacterial metallothionein gene smtA: identification of a Zn inhibited DNA-protein complex. Nucl. Acids Res. 21, 921–925 (1993)10.1093/nar/21.4.921Search in Google Scholar

Naik M.M., Pandey A., Dubey S.K.: Pseudomonas aeruginosa strain WI-1 from Mandovi estuary possesses metallothionein to alleviate lead toxicity and promotes plant growth. Ecotoxicol. Environ. Saf. 79, 129–133 (2012)Search in Google Scholar

Olafson R.W., Abel K., Sim R.G.: Prokaryotic metallothionein: preliminary characterization of a blue-green alga heavy metal-binding protein. Biochem. Biophys. Res. Commun. 89, 36–43 (1979)Search in Google Scholar

Olafson R.W., Loya S., Sim R.G.: Physiological parameters of prokaryotic metallothionein induction. Biochem. Biophys. Res. Commun. 95, 1495–1503 (1980)Search in Google Scholar

Olafson R.W., McCubbin W.D., Kay C.M.: Primary- and secondary-structural analysis of a unique prokaryotic metallothionein from a Synechococcus sp. cyanobacterium. Biochem. J. 251, 691–699 (1988)Search in Google Scholar

Palmer C.M., Guerinot M.L.: Facing the challenges of Cu, Fe and Zn homeostasis in plants. Nat. Chem. Biol. 5, 333–340 (2009)Search in Google Scholar

Pedersen M., Larsen A., Stoltenberg M., Penkova M.: Cell death in the injured brain: Roles of metallothioneins. Prog. Histochem. Cytochem. 44, 1–27 (2009)Search in Google Scholar

Pedersen M., Larsen A., Stoltenberg M., Penkova M.: The role of metallothionein in oncogenesis and cancer prognosis. Prog. Histochem. Cytochem. 44, 29–64 (2009)Search in Google Scholar

Robinson N.J., Tommey A.M., Kuske C., Jackson P.J.: Plant metallothioneins. Biochem. J. 295, 1–10 (1993)Search in Google Scholar

Robinson N.J., Whitehall S.K., Cavet J.S.: Microbial metallothioneins. Adv. Microb. Physiol. 44, 183–213 (2001)Search in Google Scholar

Rowland J.L., Niederweis M.: Resistance mechanism of Mycobacterium tuberculosis against phagosomal copper overload. Tuberculosis, 92, 202–210 (2012)10.1016/j.tube.2011.12.006Search in Google Scholar

Shi J., Lindsay W.P., Huckle J.W., Morby A.P., Robinson N.J.: Cyanobacterial metallothionein gene expressed in Escherichia coli. Metal-binding properties of the expressed protein. FEBS Lett. 2–3, 159–163 (1992)10.1016/0014-5793(92)80509-FSearch in Google Scholar

Shimizu T., Hiyama T., Ikeuchi M., Inoue Y.: Nucleotide sequence of a metallothionein gene of the thermophilic cyanobacterium Synechococcus vulcanus. Plant Mol. Biol. 20, 565–567 (1992)Search in Google Scholar

Silver S., Phung L.T.: Bacterial heavy metal resistance: new surprises. Annu. Rev. Microbiol. 50, 753–789 (1996)10.1146/annurev.micro.50.1.7538905098Search in Google Scholar

Stępkowska I.M.: Właściwości biologiczne metalotionein i ich udział w procesach oksydoredukcyjnych w komórkach, ze szczególnym uwzględnieniem ośrodkowego układu nerwowego człowieka. Post. Biol. Kom. 37, 869–885 (2010)Search in Google Scholar

Sutherland D.E., Stillman M.J.: The “magic numbers” of metallothionein. Metallomics, 3, 444–463 (2011)10.1039/c0mt00102c21409206Search in Google Scholar

Thelwell C., Robinson N.J., Turner-Cavet J.S.: An SmtB-like repressor from Synechocystis PCC 6803 regulates a zinc exporter. Proc. Natl. Acad. Sci. USA, 95, 10728–10733 (1998)10.1073/pnas.95.18.10728279639724772Search in Google Scholar

Turner J.S., Glands P.D., Samson A.C.R., Robinson N.J.: Zn2+-Sensing by the cyanobacterial metallothionein repressor SmtB: different motifs mediate metal-induced protein-DNA dissociation. Nucl. Acids Res. 24, 3714–3721 (1996)10.1093/nar/24.19.37141461718871549Search in Google Scholar

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

Vašák M.: Advances in metallothionein structure and functions. J. Trace Elem. Med. Biol. 19, 13–17 (2005)Search in Google Scholar

Waldron K.J., Robinson N.J.: How do bacterial cells ensure that metalloproteins get the correct metal? Nat. Rev. Microbiol. 7, 25–35 (2009)Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo