Skip to main content

Advertisement

Log in

Survival in amoeba—a major selection pressure on the presence of bacterial copper and zinc resistance determinants? Identification of a “copper pathogenicity island”

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

The presence of metal resistance determinants in bacteria usually is attributed to geological or anthropogenic metal contamination in different environments or associated with the use of antimicrobial metals in human healthcare or in agriculture. While this is certainly true, we hypothesize that protozoan predation and macrophage killing are also responsible for selection of copper/zinc resistance genes in bacteria. In this review, we outline evidence supporting this hypothesis, as well as highlight the correlation between metal resistance and pathogenicity in bacteria. In addition, we introduce and characterize the “copper pathogenicity island” identified in Escherichia coli and Salmonella strains isolated from copper- and zinc-fed Danish pigs.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Aarestrup FM, Cavaco L, Hasman H (2010) Decreased susceptibility to zinc chloride is associated with methicillin resistant Staphylococcus aureus CC398 in Danish swine. Vet Microbiol 142:455–457. doi:10.1016/j.vetmic.2009.10.021

    Article  CAS  PubMed  Google Scholar 

  • Aurass P, Prager R, Flieger A (2011) EHEC/EAEC O104:H4 strain linked with the 2011 German outbreak of haemolytic uremic syndrome enters into the viable but non-culturable state in response to various stresses and resuscitates upon stress relief. Environ Microbiol 13:3139–3148. doi:10.1111/j.1462-2920.2011.02604.x

    Article  PubMed  Google Scholar 

  • Aviv G, Tsyba K, Steck N, Salmon-Divon M, Cornelius A, Rahav G, Grassl GA, Gal-Mor O (2014) A unique megaplasmid contributes to stress tolerance and pathogenicity of an emergent Salmonella enterica serovar Infantis strain. Environ Microbiol 16:977–994. doi:10.1111/1462-2920.12351

    Article  CAS  PubMed  Google Scholar 

  • Baldan R, Testa F, Lore NI, Bragonzi A, Cichero P, Ossi C, Biancardi A, Nizzero P, Moro M, and Cirillo DM (2012) Factors contributing to epidemic MRSA clones replacement in a hospital setting. PLoS One, e43153. doi:10.1371/journal.pone.0043153

  • Baldan R, Rancoita PM, Di Serio C, Mazzotti M, Cichero P, Ossi C, Biancardi A, Nizzero P, Saracco A, Scarpellini P, Cirillo DM (2015) Epidemic MRSA clone ST22-IV is more resistant to multiple host- and environment-related stresses compared with ST228-I. J Antimicrob Chemother 70:757–765. doi:10.1093/jac/dku467

    Article  PubMed  Google Scholar 

  • Bonis M, Ecobichon C, Guadagnini S, Prevost MC, Boneca IG (2010) A M23B family metallopeptidase of Helicobacter pylori required for cell shape, pole formation and virulence. Mol Microbiol 78:809–819. doi:10.1111/j.1365-2958.2010.07383.x

    Article  CAS  PubMed  Google Scholar 

  • Braymer JJ, Giedroc DP (2014) Recent developments in copper and zinc homeostasis in bacterial pathogens. Curr Opin Chem Biol 19:59–66. doi:10.1016/j.cbpa.2013.12.021

    Article  CAS  PubMed  Google Scholar 

  • Brown NL, Barrett SR, Camakaris J, Lee BT, Rouch DA (1995) Molecular genetics and transport analysis of the copper-resistance determinant (pco) from Escherichia coli plasmid pRJ1004. Mol Microbiol 17:1153–1166

    Article  CAS  PubMed  Google Scholar 

  • Burlando B, Evangelisti V, Dondero F, Pons G, Camakaris J, Viarengo A (2002) Occurrence of Cu-ATPase in Dictyostelium: possible role in resistance to copper. Biochem Biophys Res Commun 291:476–483. doi:10.1006/bbrc.2002.6463

    Article  CAS  PubMed  Google Scholar 

  • Cerasi M, Liu JZ, Ammendola S, Poe AJ, Petrarca P, Pesciaroli M, Pasquali P, Raffatellu M, Battistoni A (2014) The ZupT transporter plays an important role in zinc homeostasis and contributes to Salmonella enterica virulence. Metallomics 6:845–853. doi:10.1039/c3mt00352c

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chaturvedi KS, Hung CS, Giblin DE, Urushidani S, Austin AM, Dinauer MC, Henderson JP (2014) Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic. ACS Chem Biol 9:551–561. doi:10.1021/cb400658k

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen YT, Chang HY, Lai YC, Pan CC, Tsai SF, Peng HL (2004) Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43. Gene 337:189–198. doi:10.1016/j.gene.2004.05.008

  • Cho K, Arimoto T, Igarashi T, Yamamoto M (2013) Involvement of lipoprotein PpiA of Streptococcus gordonii in evasion of phagocytosis by macrophages. Mol Oral Microbiol 28:379–391. doi:10.1111/omi.12031

    Article  CAS  PubMed  Google Scholar 

  • Crossman LC, Chaudhuri RR, Beatson SA, Wells TJ, Desvaux M, Cunningham AF, Petty NK, Mahon V, Brinkley C, Hobman CL, Savarino SJ, Turner SM, Pallen MJ, Penn CW, Parkhill J, Turner AK, Johnson TJ, Thomson NR, Smith SG, Henderson IR (2010) A commensal gone bad: complete genome sequence of the prototypical enterotoxigenic Escherichia coli strain H10407. J Bacteriol 192:5822–5831. doi:10.1128/JB.00710-10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dupont CL, Grass G, Rensing C (2011) Copper toxicity and the origin of bacterial resistance—new insights and applications. Metallomics 3:1109–1118. doi:10.1039/c1mt00107h

    Article  CAS  PubMed  Google Scholar 

  • Festa RA, Thiele DJ (2012) Copper at the front line of the host-pathogen battle. PLoS Pathog 8:e1002887. doi:10.1371/journal.ppat.1002887

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Festa RA, Helsel ME, Franz KJ, Thiele DJ (2014) Exploiting innate immune cell activation of a copper-dependent antimicrobial agent during infection. Chem Biol 21:977–987. doi:10.1016/j.chembiol.2014.06.009

    Article  CAS  PubMed  Google Scholar 

  • Fodah RA, Scott JB, Tam HH, Yan P, Pfeffer TL, Bundschuh R, Warawa JM (2014) Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model. PLoS One 9:e107394. doi:10.1371/journal.pone.0107394

    Article  PubMed Central  PubMed  Google Scholar 

  • Gehring AM, DeMoll E, Fetherston JD, Mori I, Mayhew GF, Blattner FR, Walsh CT, Perry RD (1998) Iron acquisition in plague: modular logic in enzymatic biogenesis of yersiniabactin by Yersinia pestis. Chem Biol 5:573–586

    Article  CAS  PubMed  Google Scholar 

  • German N, Doyscher D, Rensing C (2013) Bacterial killing in macrophages and amoeba: do they all use a brass dagger? Future Microbiol 8:1257–1264. doi:10.2217/fmb.13.100

    Article  CAS  PubMed  Google Scholar 

  • Gilmour MW, Thomson NR, Sanders M, Parkhill J, Taylor DE (2004) The complete nucleotide sequence of the resistance plasmid R478: defining the backbone components of incompatibility group H conjugative plasmids through comparative genomics. Plasmid 52:182–292

    Article  CAS  PubMed  Google Scholar 

  • Gradassi M, Pesciaroli M, Martinelli N, Ruggeri J, Petrucci P, Hassan WH, Raffatellu M, Scaglione FE, Ammendola S, Battistoni A, Alborali GL, Pasquali P (2013) Attenuated Salmonella enterica serovar Typhimurium lacking the ZnuABC transporter: an efficacious orally-administered mucosal vaccine against salmonellosis in pigs. Vaccine 31:3695–3701. doi:10.1016/j.vaccine.2013.05.105

    Article  CAS  PubMed  Google Scholar 

  • Gullberg E, Albrecht LM, Karlsson C, Sandegren L, Andersson DI (2014) Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals. MBio 5:e01918

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gupta A, Matsui K, Lo JF, Silver S (1999) Molecular basis for resistance to silver cations in Salmonella. Nat Med 5:183–188. doi:10.1038/5545

    Article  CAS  PubMed  Google Scholar 

  • Haeili M, Moore C, Davis CJ, Cochran JB, Shah S, Shrestha TB, Zhang Y, Bossmann SH, Benjamin WH, Kutsch O, Wolschendorf F (2014) Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 58:3727–3736. doi:10.1128/AAC.02316-13

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hasman H (2005) The tcrB gene is part of the tcrYAZB operon conferring copper resistance in Enterococcus faecium and Enterococcus faecalis. Microbiology 151:3019–3025

    Article  CAS  PubMed  Google Scholar 

  • Hobman JL, Crossman LC (2015) Bacterial antimicrobial metal ion resistance. J Med Microbiol. 64:471–497. doi:10.1099/jmm.0.023036-0

  • Hood MI, Skaar EP (2012) Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol 10:525–537. doi:10.1038/nrmicro2836

    Article  CAS  PubMed  Google Scholar 

  • Johnson TJ, Siek KE, Johnson SJ, Nolan LK (2005) DNA sequence and comparative genomics of pAPEC-O2-R, an avian pathogenic Escherichia coli transmissible R plasmid. Antimicrob Agents Chemother 49:4681–4688

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kashyap DR, Rompca A, Gaballa A, Helmann JD, Chan J, Chang CJ, Hozo I, Gupta D, Dziarski R (2014) Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress. PLoS Pathog 10:e1004280. doi:10.1371/journal.ppat.1004280

    Article  PubMed Central  PubMed  Google Scholar 

  • Kremer AN, Hoffmann H (2012) Subtractive hybridization yields a silver resistance determinant unique to nosocomial pathogens in the Enterobacter cloacae complex. J Clin Microbiol 50:3249–3257. doi:10.1128/JCM.00885-12

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Loeffler A, McCarthy A, Lloyd DH, Musilova E, Pfeiffer DU, Lindsay JA (2013) Whole-genome comparison of meticillin-resistant Staphylococcus aureus CC22 SCCmecIV from people and their in-contact pets. Vet Dermatol 24:538–e128. doi:10.1111/vde.12062

    Article  PubMed  Google Scholar 

  • Lopes SC, Ribeiro C, Gameiro P (2013) A new approach to counteract bacteria resistance: a comparative study between moxifloxacin and a new moxifloxacin derivative in different model systems of bacterial membrane. Chem Biol Drug Des 81:265–274. doi:10.1111/cbdd.12071

    Article  CAS  PubMed  Google Scholar 

  • Lüthje FL, Hasman H, Aarestrup FM, Alwathnani HA, Rensing C (2014) Genome sequences of two copper-resistant Escherichia coli strains isolated from copper-fed pigs. Genome Announc 2:e01341. doi:10.1128/genomeA.01341-14

    Article  PubMed Central  PubMed  Google Scholar 

  • Macomber L, Imlay JA (2009) The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. Proc Natl Acad Sci U S A 106:8344–8349. doi:10.1073/pnas.0812808106

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Manning T, Mikula R, Lee H, Calvin A, Darrah J, Wylie G, Phillips D, Bythell BJ (2014) The copper (II) ion as a carrier for the antibiotic capreomycin against Mycobacterium tuberculosis. Bioorg Med Chem Lett 24:976–982. doi:10.1016/j.bmcl.2013.12.053

    Article  CAS  PubMed  Google Scholar 

  • McHugh GL, Moellering RC, Hopkins CC, Swartz MN (1975) Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin. Lancet 1:235–240

    Article  CAS  PubMed  Google Scholar 

  • Moreno Switt AI, den Bakker HC, Cummings CA, Rodriguez-Rivera LD, Govoni G, Raneiri ML, Degoricija L, Brown S, Hoelzer K, Peters JE, Bolchacova E, Furtado MR, Wiedmann M (2012) Identification and characterization of novel Salmonella mobile elements involved in the dissemination of genes linked to virulence and transmission. PLoS One 7:e41247. doi:10.1371/journal.pone.0041247

    Article  PubMed Central  PubMed  Google Scholar 

  • Mourão J, Novais C, Machado J, Peixe L, Antunes P (2015) Metal tolerance in emerging clinical relevant multidrug-resistant Salmonella enterica serotype 4,[5], 12:i:- clones circulating in Europe. Int J Antimicrob Agents 45:610–616. doi:10.1016/j.ijantimicag.2015.01.013

    Article  PubMed  Google Scholar 

  • Neyrolles O, Wolschendorf F, Mitra A, Niederweis M (2015) Mycobacteria, metals, and the macrophage. Immunol Rev 264:249–263. doi:10.1111/imr.12265

    Article  CAS  PubMed  Google Scholar 

  • Ong C-IY, Gillen CM, Walkera MJ, McEwan AG (2014) An antimicrobial role for zinc in innate immune defense against Group A Streptococcus. J Infect Dis 209:1500–1508. doi:10.1093/infdis/jiu053

    Article  CAS  PubMed  Google Scholar 

  • Ordax M, Marco-Noales E, Lopez MM, Biosca EG (2006) Survival strategy of Erwinia amylovora against copper: induction of the viable-but-nonculturable state. Appl Environ Microbiol 72:3482–3488. doi:10.1128/AEM.72.5.3482-3488.2006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pesciaroli M, Aloisio F, Ammendola S, Pistoia C, Petrucci P, Tarantino M, Francia M, Battistoni A, Pasquali P (2011) An attenuated Salmonella enterica serovar Typhimurium strain lacking the ZnuABC transporter induces protection in a mouse intestinal model of Salmonella infection. Vaccine 29:1783–1790. doi:10.1016/j.vaccine.2010.12.111

    Article  CAS  PubMed  Google Scholar 

  • Peters JE, Fricker AD, Kapili BJ, Petassi MT (2014) Heteromeric transposase elements: generators of genomic islands across diverse bacteria. Mol Microbiol 93:1084–1092. doi:10.1111/mmi.12740

    CAS  PubMed  Google Scholar 

  • Qin Y, Hasman H, Aarestrup FM, Alwathnani HA, and Rensing C (2014) Genome sequences of three highly copper-resistant Salmonella enterica subsp. I serovar Typhimurium strains isolated from pigs in Denmark. Genome Announc 2. doi:10.1128/genomeA.01334-14

  • Rakin A, Schneider L, Podladchikova O (2012) Hunger for iron: the alternative siderophore iron scavenging systems in highly virulent Yersinia. Front Cell Infect Microbiol 2:151/1. doi:10.3389/fcimb.2012.00151

    Article  Google Scholar 

  • Randall CP, Oyama LB, Bostock JM, Chopra I, O’Neill AJ (2013) The silver cation (Ag+): antistaphylococcal activity, mode of action and resistance studies. J Antimicrob Chemother 68:131–138. doi:10.1093/jac/dks372

    Article  CAS  PubMed  Google Scholar 

  • Randall CP, Gupta A, Jackson N, Busse D, O’Neill AJ (2015) Silver resistance in Gram-negative bacteria: a dissection of endogenous and exogenous mechanisms. J Antimicrob Chemother 70:1037–1046. doi:10.1093/jac/dku523

    PubMed Central  PubMed  Google Scholar 

  • Reffuveille F, Serror P, Chevalier S, Budin-Verneuil A, Ladjouzi R, Bernay B, Auffray Y, Rince A (2012) The prolipoprotein diacylglyceryl transferase (Lgt) of Enterococcus faecalis contributes to virulence. Microbiology 158:816–825. doi:10.1099/mic.0.055319-0

    Article  CAS  PubMed  Google Scholar 

  • Ren Y, Ren Y, Zhou Z, Guo X, Li Y, Feng L, Wang L (2010) Complete genome sequence of Enterobacter cloacae subsp. cloacae type strain ATCC 13047. J Bacteriol 192:2463–2464. doi:10.1128/JB.00067-10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rensing C, Ghosh M, Rosen BP (1999) Families of soft-metal-ion-transporting ATPases. J Bacteriol 181:5891–5897

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rosenzweig AC, Arguello JM (2012) Toward a molecular understanding of metal transport by P(1B)-type ATPases. Curr Top Membr 69:113–136. doi:10.1016/B978-0-12-394390-3.00005-7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sandegren L, Linkevicius M, Lytsy B, Melhus A, Andersson DI (2012) Transfer of an Escherichia coli ST131 multiresistance cassette has created a Klebsiella pneumoniae-specific plasmid associated with a major nosocomial outbreak. J Antimicrob Chemother 67:74–83. doi:10.1093/jac/dkr405

    Article  CAS  PubMed  Google Scholar 

  • Schubert S, Dufke S, Sorsa J, Heesemann J (2004) A novel integrative and conjugative element (ICE) of Escherichia coli: the putative progenitor of the Yersinia high-pathogenicity island. Mol Microbiol 51:837–848. doi:10.1046/j.1365-2958.2003.03870.x

    Article  CAS  PubMed  Google Scholar 

  • Shams S, Ali B, Afzal M, Kazmi I, Al-Abbasi FA, Anwar F (2014) Antifungal effect of gatifloxacin and copper ions combination. J Antibiot (Tokyo) 67:499–504. doi:10.1038/ja.2014.35

    Article  CAS  Google Scholar 

  • Slifierz MJ, Park J, Friendship RM, Weese JS (2014) Zinc-resistance gene CzrC identified in methicillin-resistant Staphylococcus hyicus isolated from pigs with exudative epidermitis. Can Vet J 55:489–490

    PubMed Central  PubMed  Google Scholar 

  • Speer A, Shrestha TB, Bossmann SH, Basaraba RJ, Harber GJ, Michalek SM, Niederweis M, Kutsch O, Wolschendorf F (2013) Copper-boosting compounds: a novel concept for antimycobacterial drug discovery. Antimicrob Agents Chemother 57:1089–1091. doi:10.1128/AAC.01781-12

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Subashchandrabose S, Hazen TH, Brumbaugh AR, Himpsl SD, Smith SN, Ernst RD, Rasko DA, Mobley HL (2014) Host-specific induction of Escherichia coli fitness genes during human urinary tract infection. Proc Natl Acad Sci U S A 111:18327–18332. doi:10.1073/pnas.1415959112

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wu KM, Li LH, Yan JJ, Tsao N, Liao TL, Tsai HC, Fung CP, Chen HJ, Liu YM, Wang JT, Fang CT, Chang SC, Shu HY, Liu TT, Chen YT, Shiau YR, Lauderdale TL, Su IJ, Kirby R, Tsai SF (2009) Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J Bacteriol 191:4492–4501. doi:10.1128/JB.00315-09

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 Env Microbiol 78:3614–3621. doi:10.1128/AEM.07368-11

    Article  CAS  Google Scholar 

  • Yu D, Pi B, Chen Y, Wang Y, Ruan Z, Otto M, Yu Y (2014) Characterization of the staphylococcal cassette chromosome composite island of Staphylococcus haemolyticus SH32, a methicillin-resistant clinical isolate from China. PLoS One 9:e87346. doi:10.1371/journal.pone.0087346

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhang S, Wang D, Wang Y, Hasman H, Aerestrup FM, Alwathnani HA, Zhu YG, Rensing C (2015) Genome sequences of copper resistant and sensitive Enterococcus faecalis strains isolated from copper-fed pigs. Stand. Genomic Sci (in press)

  • Zimmermann M, Udagedara SR, Sze CM, Ryan TM, Howlett GJ, Xiao Z, Wedd AG (2012) PcoE - A metal sponge expressed to the periplasm of copper resistance Escherichia coli. Implication of its function role in copper resistance. J Inorg Biochem 115:186–197. doi:10.1016/j.jinorgbio.2012.04.009

Download references

Acknowledgments

This work was supported in part by the Center for Environmental and Agricultural Microbiology (CREAM) funded by the Villum Kann Rasmussen Foundation.

Conflict of interest

The authors declare that they have no competing interests.

Compliance with ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher Rensing.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, X., Lüthje, F.L., Qin, Y. et al. Survival in amoeba—a major selection pressure on the presence of bacterial copper and zinc resistance determinants? Identification of a “copper pathogenicity island”. Appl Microbiol Biotechnol 99, 5817–5824 (2015). https://doi.org/10.1007/s00253-015-6749-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-015-6749-0

Keywords

Navigation