Skip to main content

Advertisement

SpringerLink
Log in

Gallium(III), cobalt(III) and copper(II) protoporphyrin IX exhibit antimicrobial activity against Porphyromonas gingivalis by reducing planktonic and biofilm growth and invasion of host epithelial cells

  • Short Communication
  • Published:
Archives of Microbiology Aims and scope Submit manuscript

Abstract

Porphyromonas gingivalis acquires heme for growth, and initiation and progression of periodontal diseases. One of its heme acquisition systems consists of the HmuR and HmuY proteins. This study analyzed the antimicrobial activity of non-iron metalloporphyrins against P. gingivalis during planktonic growth, biofilm formation, epithelial cell adhesion and invasion, and employed hmuY, hmuR and hmuY-hmuR mutants to assess the involvement of HmuY and HmuR proteins in the acquisition of metalloporphyrins. Iron(III) mesoporphyrin IX (mesoheme) and iron(III) deuteroporphyrin IX (deuteroheme) supported planktonic growth of P. gingivalis cells, biofilm accumulation, as well as survival, adhesion and invasion of HeLa cells in a way analogous to protoheme. In contrast, cobalt(III), gallium(III) and copper(II) protoporphyrin IX exhibited antimicrobial activity against P. gingivalis, and thus represent potentially useful antibacterial compounds with which to target P. gingivalis. P. gingivalis hmuY, hmuR and hmuY-hmuR mutants showed decreased growth and infection of epithelial cells in the presence of all metalloporphyrins examined. In conclusion, the HmuY protein may not be directly involved in transport of free metalloporphyrins into the bacterial cell, but it may also play a protective role against metalloporphyrin toxicity by binding an excess of these compounds.

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

Fig. 1
Fig. 2
Fig. 3

References

  • Bozja J, Yi K, Shafer WM, Stojiljkovic I (2004) Porphyrin-based compounds exert antibacterial action against the sexually transmitted pathogens Neisseria gonorrhoeae and Haemophilus ducreyi. Int J Antimicrob Agents 24:578–584

    Article  PubMed  CAS  Google Scholar 

  • Bramanti TE, Holt SC (1991) Roles of porphyrins and host iron transport proteins in regulation of growth of Porphyromonas gingivalis W50. J Bacteriol 173:7330–7339

    PubMed  CAS  Google Scholar 

  • Craig RG, Yip YK, So MK, Boylan RJ, Socransky SS, Haffajee AD (2003) Relationship of destructive periodontal disease to the acute-phase response. J Periodontol 74:1007–1016

    Article  PubMed  Google Scholar 

  • Curtis MA, Griffiths GS, Price SJ, Coulthurst SK, Johnson NW (1988) Detection of high-risk groups and individuals for periodontal diseases. Clinical assessment of the periodontium. J Clin Periodontol 15:628–632

    Article  PubMed  CAS  Google Scholar 

  • Fuller MD, Caldwell DR (1982) Tetrapyrrole utilization by Bacteroides fragilis. Can J Microbiol 28:1304–1310

    Article  PubMed  CAS  Google Scholar 

  • Gao JL, Nguyen KA, Hunter N (2010) Characterization of a hemophore-like protein from Porphyromonas gingivalis. J Biol Chem 285:40028–40038

    Article  PubMed  CAS  Google Scholar 

  • Graves DT, Jiang Y, Genco CA (2000) Periodontal disease: bacterial virulence factors, host response and impact on systemic health. Curr Opin Infect Dis 13:227–232

    Article  PubMed  CAS  Google Scholar 

  • Krewulak KD, Vogel HJ (2008) Structural biology of bacterial iron uptake. Biochim Biophys Acta 1778:1781–1804

    Article  PubMed  CAS  Google Scholar 

  • Kuboniwa M, Hendrickson EL, Xia Q, Wang T, Xie H, Hackett M, Lamont RJ (2009) Proteomics of Porphyromonas gingivalis within a model oral microbial community. BMC Microbiol 9:98

    Article  PubMed  Google Scholar 

  • Lamont RJ, Chan A, Belton CM, Izutsu KT, Vasel D, Weinberg A (1995) Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun 63:3878–3885

    PubMed  CAS  Google Scholar 

  • Leon R, Silva N, Ovalle A, Chaparro A, Ahumada A, Gajardo M, Martinez M, Gamonal J (2007) Detection of Porphyromonas gingivalis in the amniotic fluid in pregnant women with a diagnosis of threatened premature labor. J Periodontol 78:1249–1255

    Article  PubMed  Google Scholar 

  • Marsh PD (2004) Dental plaque as a microbial biofilm. Caries Res 38:204–211

    Article  PubMed  CAS  Google Scholar 

  • McCall DR, Caldwell DR (1977) Tetrapyrrole utilization by Bacteroides ruminicola. J Bacteriol 131:809–814

    PubMed  CAS  Google Scholar 

  • Meurman JH, Sanz M, Janket SJ (2004) Oral health, atherosclerosis, and cardiovascular disease. Crit Rev Oral Biol Med 15:403–413

    Article  PubMed  Google Scholar 

  • Nakagawa I, Inaba H, Yamamura T, Kato T, Kawai S, Ooshima T, Amano A (2006) Invasion of epithelial cells and proteolysis of cellular focal adhesion components by distinct types of Porphyromonas gingivalis fimbriae. Infect Immun 74:3773–3782

    Article  PubMed  CAS  Google Scholar 

  • Olczak T, Dixon DW, Genco CA (2001) Binding specificity of the Porphyromonas gingivalis heme and hemoglobin receptor HmuR, gingipain K, and gingipain R1 for heme, porphyrins, and metalloporphyrins. J Bacteriol 183:5599–5608

    Article  PubMed  CAS  Google Scholar 

  • Olczak T, Simpson W, Liu X, Genco CA (2005) Iron and heme utilization in Porphyromonas gingivalis. FEMS Microbiol Rev 29:119–144

    Article  PubMed  CAS  Google Scholar 

  • Olczak T, Sroka A, Potempa J, Olczak M (2008) Porphyromonas gingivalis HmuY and HmuR—further characterization of a novel mechanism of heme utilization. Arch Microbiol 183:197–210

    Article  Google Scholar 

  • Olczak T, Wojtowicz H, Ciuraszkiewicz J, Olczak M (2010) Species specificity, surface exposure, protein expression, immunogenicity, and participation in biofilm formation of Porphyromonas gingivalis HmuY. BMC Microbiol 10:134

    Article  PubMed  Google Scholar 

  • Paramaesvaran M, Nguyen KA, Caldon E, McDonald JA, Najdi S, Gonzaga G, Langley DB, DeCarlo A, Crossley MJ, Hunter N, Collyer CA (2003) Porphyrin-mediated cell surface heme capture from hemoglobin by Porphyromonas gingivalis. J Bacteriol 185:2528–2537

    Article  PubMed  CAS  Google Scholar 

  • Rosenstein ED, Greenwald RA, Kushner LJ, Weissmann G (2004) Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation 28:311–318

    Article  PubMed  Google Scholar 

  • Roth GA, Ankersmit HJ, Brown VB, Papapanou PN, Schmidt AM, Lalla E (2007) Porphyromonas gingivalis infection and cell death in human aortic endothelial cells. FEMS Microbiol Lett 272:106–113

    Article  PubMed  CAS  Google Scholar 

  • Smalley JW, Birss AJ, Silver J (2000) The periodontal pathogen Porphyromonas gingivalis harnesses the chemistry of the μ-oxo bishaem of iron protoporphyrin IX to protect against hydrogen peroxide. FEMS Microbiol Lett 183:159–164

    PubMed  CAS  Google Scholar 

  • Smalley JW, Silver J, Birss AJ, Withnall R, Titler PJ (2003) The heam pigment of the oral anaerobes Prevotella nigrescens and Prevotella intermedia is composed of iron(III) protoporphyrin IX in the monomeric form. Microbiology 149:1711–1718

    Article  PubMed  CAS  Google Scholar 

  • Smalley JW, Byrne DP, Birss AJ, Wojtowicz H, Sroka A, Potempa J, Olczak T (2011) HmuY haemophore and gingipain proteases constitute a unique syntrophic system of haem acquisition by Porphyromonas gingivalis. PLoS ONE 6(2):e17182

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Wojaczynski J, Wojtowicz H, Bielecki M, Olczak M, Smalley JW, Latos-Grazynski L, Olczak T (2011) Iron(III) mesoporphyrin IX and iron(III) deuteroporphyrin IX bind to the Porphyromonas gingivalis HmuY hemophore. Biochem Biophys Res Commun 411:299–304

    Article  PubMed  CAS  Google Scholar 

  • Wojtowicz H, Guevara T, Tallant C, Olczak M, Sroka A, Potempa J, Sola M, Olczak T, Gomis-Ruth FX (2009a) Unique structure and stability of HmuY, a novel heme-binding protein of Porphyromonas gingivalis. PLoS Pathog 5(5):e100041

    Article  Google Scholar 

  • Wojtowicz H, Wojaczynski J, Olczak M, Kroliczewski J, Latos-Grazynski L, Olczak T (2009b) Heme environment in HmuY, the heme-binding protein of Porphyromonas gingivalis. Biochem Biophys Res Commun 383:178–182

    Article  PubMed  CAS  Google Scholar 

  • Yilmaz O, Verbeke P, Lamont RJ, Ojcius DM (2006) Intercellular spreading of Porphyromonas gingivalis infection in primary gingival epithelial cells. Infect Immun 74:703–710

    Article  PubMed  CAS  Google Scholar 

  • Yukitake H, Naito M, Sato K, Shoji M, Ohara N, Yoshimura M, Sakai E, Nakayama K (2011) Effects of non-iron metalloporphyrins on growth and gene expression of Porphyromonas gingivalis. Microbiol Immunol 55:141–153

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants nos. N401 029 32/0742 and N N303 518438 from the Department of Scientific Research, Ministry of Science and Higher Education and by Wroclaw Research Center EIT + under the project “Biotechnologies and advanced medical technologies—BioMed” (POIG 01.01.02-02-003/08/00) financed from the European Regional Development Fund (Operational Program Innovative Economy, 1.1.2) (TO). Part of the data was presented at 88th IADR General Session, Barcelona, Spain, 14–17 July 2010.

Author information

Authors and Affiliations

  1. Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137, Wroclaw, Poland

    Teresa Olczak, Dorota Maszczak-Seneczko & Mariusz Olczak

  2. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Apex Building, 8 West Derby Street, Liverpool, L69 7BE, UK

    John W. Smalley

Authors
  1. Teresa Olczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dorota Maszczak-Seneczko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John W. Smalley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mariusz Olczak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teresa Olczak.

Additional information

Communicated by Sebastian Suerbaum.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Olczak, T., Maszczak-Seneczko, D., Smalley, J.W. et al. Gallium(III), cobalt(III) and copper(II) protoporphyrin IX exhibit antimicrobial activity against Porphyromonas gingivalis by reducing planktonic and biofilm growth and invasion of host epithelial cells. Arch Microbiol 194, 719–724 (2012). https://doi.org/10.1007/s00203-012-0804-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00203-012-0804-3

Keywords

Search

Navigation