Skip to main content

Advertisement

SpringerLink
Log in

Comparative photodynamic inactivation of antibiotic resistant bacteria by first and second generation cationic photosensitizers

  • Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Photodynamic inactivation (PDI) is an efficient approach against a wide range of microorganisms and can be viewed as an alternative for the treatment of microbial infections. In this work we synthesized “first” and “second” generation photosensitizers (PSs), the tetra-cationic porphyrin 2b and the new penta-cationic chlorin 3b, respectively, and evaluated their efficiency against two antibiotic resistant bacterial strains, Staphylococcus aureus and Pseudomonas aeruginosa. The PS 3b was obtained in very good yield by an easy synthesis method. The PDI studies were performed in parallel with 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (1), a widely studied PS in PDI, and the obtained results were compared. Two different light ranges were used: white light (400–800 nm) and red light (530–800 nm) delivered at a fluence rate of 150 mW cm−2. The results show that both strains, even though antibiotic resistant, were efficiently inactivated by the three PSs, chlorin 3b being the most effective. For the Gram positive bacterium S. aureus a 7.0 log reduction was observed after 5–10 min of irradiation, at a concentration of 0.5 μM, whereas for the Gram negative P. aeruginosa, similar photoinactivation occurred at a higher PS concentration (10 μM) and after a longer irradiation period (30 min). The synthetic chlorin 3b can be regarded as promising for the treatment of bacterial infections under red light, which penetrates deeper in living tissues. The results of this study open the possibility to prepare a new series of chlorin-type derivatives to efficiently photoinactivate Gram (+) and (−) antibiotic resistant bacteria. The efficient PDI with the chlorin 3b indicates high potential for the use of a TPPF20 scaffold in the preparation of new generation PSs based on cationic chlorin derivatives.

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

Notes and references

  1. A. Almeida, A. Cunha, M. A. F. Faustino, A. C. Tomé and M. G. P. M. S. Neves, Porphyrins as antimicrobial photosensitizing agents, in Photodynamic Inactivation of Microbial Pathogens: Medical and Environmental Applications, ed. M. R. Hamblin and G. Jori, Royal Society of Chemistry, Padova, 2011, p. 83.

    Chapter  Google Scholar 

  2. S. Banfi, Caruso, E. Buccafurni, L. Battini, V. S. Zazzaron, P. Barbieri and V. Orlandi, Antibacterial activity of tetraaryl-porphyrin photosensitizers: an in vitro study on Gram negative and Gram positive bacteria, J. Photochem. Photobiol., B, 2006, 85, 28.

    Article  CAS  Google Scholar 

  3. Y. S. Park, H. B. Lee, S. Chin, S. H. Han, S. G. Hong, S. K. Hong, H. Y. Kim, Y. Uh, H. B. Shin, E. J. Choo, S. H. Han, W. Song, S. H. Jeong, K. Lee and J. M. Kim, Acquisition of extensive drug-resistant Pseudomonas aeruginosa among hospitalized patients: risk factors and resistance mechanisms to carbapenems, J. Hosp. Infect., 2011, 79, 54.

    Article  CAS  PubMed  Google Scholar 

  4. A. Giedraitienė, A. Vitkauskienė, R. Naginienė and A. Pavilonis, Antibiotic resistance mechanisms of clinically important bacteria, Medicina, 2011, 47, 137.

    Article  PubMed  Google Scholar 

  5. L. Costa, J. P. C. Tomé, M. G. P. M. S. Neves, A. C. Tomé, J. A. S. Cavaleiro, M. A. F. Faustino, A. Cunha, N. C. M. Gomes and A. Almeida, Evaluation of resistance development and viability recovery by a non-enveloped virus after repeated cycles of aPDT, Antiviral Res., 2011, 91, 278.

    Article  CAS  PubMed  Google Scholar 

  6. J. Nakonieczna, E. Michta, M. Rybicka, M. Grinholc, A. Gwizdek-Wiśniewska and K. P. Bielawski, Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment, BMC Microbiol., 2010, 10, 323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. A. Tavares, C. M. B. Carvalho, M. A. Faustino, M. G. M. S. Neves, J. P. C. Tomé, A. C. Tomé, J. A. S. Cavaleiro, A. Cunha, N. C. M. Gomes, E. Alves and A. Almeida, Antimicrobial photodynamic therapy: study of bacterial recovery viability and potential development of resistance after treatment, Mar. Drugs, 2010, 8, 91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. D. A. Caminos, M. B. Spesia, P. Pons and E. N. Durantini, Mechanisms of Escherichia coli photodynamic inactivation by an amphiphilic tricationic porphyrin and 5,10,15,20-tetra(4-N,N,N trimethylammoniumphenyl) porphyrin, Photochem. Photobiol. Sci., 2008, 7, 1071.

    Article  CAS  PubMed  Google Scholar 

  9. M. R. Hamblin and T. Hasan, Photodynamic therapy: a new antimicrobial approach to infectious disease?, Photochem. Photobiol. Sci., 2004, 3, 436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. J. L. Wardlaw, T. J. Sullivan, C. N. Lux and F. W. Austin, Photodynamic therapy against common bacteria causing wound and skin infections, Vet. J., 2012, 192, 374.

    Article  CAS  PubMed  Google Scholar 

  11. W. Hongcharu, C. Taylor, Y. Chang, D. Aghassi, K. Suthamjariya and R. Anderson, Topical ALA-photodynamic therapy for the treatment of acne vulgaris, J. Invest. Dermatol., 2000, 15, 183.

    Article  Google Scholar 

  12. Y. Itoh, Y. Ninomiya, S. Tajima and A. Ishibashi, Photodynamic therapy for acne vulgaris with topical 5-aminolevulinic acid, Arch. Dermatol., 2000, 136, 1093.

    Article  CAS  PubMed  Google Scholar 

  13. G. B. Kharkwal, S. K. Sharma, Y. Y. Huang, T. Dai and M. R. Hamblin, Photodynamic therapy for infections: clinical applications, Lasers Surg. Med., 2011, 43, 755.

    Article  PubMed  PubMed Central  Google Scholar 

  14. N. Kömerik and M. Wilson, Factors influencing the susceptibility of Gram-negative bacteria to toluidine blue O-mediated lethal photosensitization, J. Appl. Microbiol., 2002, 92, 618.

    Article  PubMed  Google Scholar 

  15. M. Wainwright, D. A. Phoenix, J. Marland, D. R. A. Wareing and F. J. Bolton, A study of photobactericidal activity in the phenothiazinium series, FEMS Immunol. Med. Microbiol., 1997, 19, 75.

    Article  CAS  PubMed  Google Scholar 

  16. D. A. Phoenix, Z. Sayed, S. Hussain, F. Harris and M. Wainwright, The phototoxicity of phenothiazinium derivatives against Escherichia coli and Staphylococcus aureus, FEMS Immunol. Med. Microbiol., 2003, 39, 1.

    Article  CAS  Google Scholar 

  17. T. N. Demidova and M. R. Hamblin, Photodynamic therapy targeted to pathogens, Int. J. Immunopathol. Pharmacol., 2004, 17, 245.

    Article  CAS  PubMed  Google Scholar 

  18. J. P. C. Tomé, E. M. P. Silva, A. M. V. M. Pereira, C. M. A. Alonso, M. A. F. Faustino, M. G. M. S. Neves, A. C. Tomé, J. A. S. Cavaleiro, S. A. P. Tavares, R. R. Duarte, M. F. Caeiro and M. L. Valdeira, Synthesis of neutral and cationic tripyridylporphyrin-d-galactose conjugates and the photoinactivation of HSV-1, Bioorg. Med. Chem., 2007, 15, 4705.

    Article  PubMed  CAS  Google Scholar 

  19. M. C. Gomes, S. M. Woranovicz-Barreira, M. A. F. Faustino, R. Fernandes, M. G. P. M. S. Neves, A. C. Tomé, N. C. M. Gomes, A. Almeida, J. A. S. Cavaleiro, A. Cunha, J. P. C. Tomé, Photodynamic inactivation of Penicillium chrysogenum conidia by cationic porphyrins, Photochem. Photobiol. Sci., 2011, 10, 1735.

    Article  CAS  PubMed  Google Scholar 

  20. J. P. C. Tomé, M. G. P. M. S. Neves, A. C. Tomé, J. A. S. Cavaleiro, A. F. Mendonça, I. N. Pegado, R. Duarte and M. L. Valdeira, Synthesis of glycoporphyrin derivatives and their antiviral activity against herpes simplex virus types 1 and 2, Bioorg. Med. Chem., 2005, 13, 3878.

    Article  PubMed  CAS  Google Scholar 

  21. C. M. B. Carvalho, A. T. P. C. Gomes, S. C. Fernandes, A. C. B. Prata, M. A. F. Faustino, J. P. C. Tomé, M. G. P. M. S. Neves, A. C. Tomé, Z. Lin, J. P. Rainho, A. Almeida, A. Cunha, J. Rocha and J. A. S. Cavaleiro, Photoinactivation of bacteria in wastewater by porphyrins: bacterial β-galactosidase activity and leucine-uptake as methods to monitor the process, J. Photochem. Photobiol., B, 2007, 88, 112.

    Article  CAS  Google Scholar 

  22. J. P. C. Tomé, M. G. P. M. S. Neves, A. C. Tomé, J. A. S. Cavaleiro, M. Soncin, M. Magaraggia, S. Ferro and G. Jori, Synthesis and antibacterial activity of new poly-S-lysine-porphyrin conjugates, J. Med. Chem., 2004, 47, 6649.

    Article  PubMed  CAS  Google Scholar 

  23. E. Alves, L. Costa, C. Carvalho, J. P. C. Tomé, M. A. F. Faustino, M. G. P. M. S. Neves, A. C. Tomé, J. A. S. Cavaleiro, A. Cunha and A. Almeida, Charge effect on the photoinactivation of Gram negative and Gram positive bacteria by cationic meso-substituted porphyrins, BMC Microbiol., 2009, 9, 70.

    Article  PubMed  PubMed Central  Google Scholar 

  24. L. Costa, E. Alves, C. M. B. Carvalho, J. P. C. Tomé, M. A. F. Faustino, M. G. P. M. S. Neves, A. C. Tomé, J. A. S. Cavaleiro, A. Cunha and A. Almeida, Sewage bacteriophage photoinactivation by cationic porphyrins: a study of charge effect, Photochem. Photobiol. Sci., 2008, 7, 415.

    Article  CAS  PubMed  Google Scholar 

  25. J. Gil-Tomás, L. Dekker, N. Narband, I. P. Parkin, S. P. Nair, C. Street and M. J. Wilson, Lethal photosensitisation of bacteria using a tin chlorin e6–glutathione–gold nanoparticle conjugate, J. Mater. Chem., 2011, 21, 4189.

    Article  CAS  Google Scholar 

  26. L. Huang, T. Zhiyentayev, Y. Xuan, D. Azhibek, G. B. Kharkwal and M. R. Hamblin, Photodynamic inactivation of bacteria using polyethylenimine–chlorin(e6) conjugates: effect of polymer molecular weight, substitution ratio of chlorin(e6) and pH, Lasers Surg. Med., 2011, 43, 313.

    Article  PubMed  PubMed Central  Google Scholar 

  27. T. Dai, G. P. Tegos, Z. Lu, L. Huang, T. Zhiyentayev, M. J. Franklin, D. G. Baer and M. R. Hamblin, Photodynamic therapy for Acinetobacter baumannii burn infections in mice, Antimicrob. Agents Chemother., 2009, 53, 3929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. S. Kranz, A. Guellmar, A. Völpel, B. Gitter, V. Albrecht and B. W. Sigusch, Photodynamic suppression of Enterococcus faecalis using the photosensitizer mTHPC, Lasers Surg. Med., 2011, 43, 241.

    Article  PubMed  Google Scholar 

  29. G. P. Tegos, M. Anbe, C. Yang, T. N. Demidova, M. Satti, P. Mroz, S. Janjua, F. Gad and M. R. Hamblin, Protease-stable polycationic photosensitizer conjugates between polyethyleneimine and chlorin(e6) for broad-spectrum antimicrobial photoinactivation, Antimicrob. Agents Chemother., 2006, 50, 1402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. N. S. Soukos, M. R. Hamblin and T. Hasan, The effect of charge on cellular uptake and phototoxicity of polylysine chlorin conjugates, Photochem. Photobiol., 1997, 65, 723.

    Article  CAS  PubMed  Google Scholar 

  31. J. Park, Y. Moon, I. Bang, Y. Kim, S. Kim and J. Yoon, Antimicrobial effect of photodynamic therapy using a highly pure chlorin e6, Lasers Med. Sci., 2010, 25, 705.

    Article  PubMed  Google Scholar 

  32. M. R. Hamblin, S. K. Sharmaa and G. B. Kharkwal, Innovative design of antimicrobial photosensitizers, in Photodynamic Inactivation of Microbial Pathogens: Medical and Environmental Applications, ed. M. R. Hamblin and G. Jori, Royal Society of Chemistry, Padova, 2011, p. 69.

    Chapter  Google Scholar 

  33. Y. Nitzan and I. Pechatnikov, Approaches to kill gram negative bacteria by photosensitized processes, in Photodynamic Inactivation of Microbial Pathogens: Medical and Environmental Applications, ed. M. R. Hamblin and G. Jori, Royal Society of Chemistry, Padova, 2011, p. 45.

    Chapter  Google Scholar 

  34. V. Engelhardt, B. Krammer and K. Plaetzer, Antibacterial photodynamic therapy using water-soluble formulations of hypericin or mTHPC is effective in inactivation of Staphylococcus aureus, Photochem. Photobiol. Sci., 2010, 9, 365.

    Article  CAS  PubMed  Google Scholar 

  35. S. Schastak, S. Ziganshyna, B. Gitter, P. Wiedemann and T. Claudepierre, Efficient photodynamic therapy against gram-positive and gram-negative bacteria using THPTS, a cationic photosensitizer excited by infrared wavelength, PLoS One, 2010, 5, 11674.

    Article  CAS  Google Scholar 

  36. S. Schastak, B. Gitter, R. Handzel, R. Hermann and P. Wiedemann, Improved photoinactivation of gram-negative and gram-positive methicillin-resistant bacterial strains using a new near-infrared absorbing meso-tetrahydroporphyrin: a comparative study with a chlorine e6 photosensitizer photolon, Methods Find. Exp. Clin. Pharmacol., 2008, 30, 129.

    Article  CAS  PubMed  Google Scholar 

  37. L. Huang, Y. Y. Huang, P. Mroz, G. P. Tegos, T. Zhiyentayev, S. K. Sharma, Z. Lu, T. Balasubramanian, M. Krayer, C. Ruzié, E. Yang, H. L. Kee, C. Kirmaier, J. R. Diers, D. F. Bocian, D. Holten, J. S. Lindsey and M. R. Hamblin, Stable synthetic cationic bacteriochlorins as selective antimicrobial photosensitizer, Antimicrob. Agents Chemother., 2010, 54, 3834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. J. B. Pereira, E. F. A. Carvalho, M. A. F. Faustino, R. Fernandes, M. G. P. M. S. Neves, J. A. S. Cavaleiro, N. C. M. Gomes, A. Cunha, A. Almeida, J. P. C. Tomé, Phthalocyaninethio-pyridinium derivatives as antibacterial photosensitizers, Photochem. Photobiol., 2012, 88, 537.

    Article  CAS  PubMed  Google Scholar 

  39. M. Soncin, C. Fabris, A. Busetti, D. Dei, D. Nistri and G. Roncucci, Approaches to selectivity in the Zn(ii)-phthalocyanine-photosensitized inactivation of wild-type and antibiotic-resistant Staphylococcus aureus, Photochem. Photobiol. Sci., 2002, 1, 815.

    Article  CAS  PubMed  Google Scholar 

  40. V. Mantareva, V. Kussovski, I. Angelov, D. Wöhrle, R. Dimitrov, E. Popova and S. Dimitrov, Non-aggregated Ga(iii)-phthalocyanines in the photodynamic inactivation of planktonic and biofilm cultures of pathogenic microorganisms, Photochem. Photobiol. Sci., 2011, 10, 91.

    Article  CAS  PubMed  Google Scholar 

  41. X. Chen, L. Hui, D. A. Foster and C. M. Drain, Efficient synthesis and photodynamic activity of porphyrin-saccharide conjugates: Targeting and incapacitating cancer cells, Biochemistry, 2004, 43, 10918.

    Article  CAS  PubMed  Google Scholar 

  42. D. Samaroo, M. Vinodu, X. Chen and C. M. Drain, meso-tetra(pentafluorophenyl) porphyrin as an efficient platform for combinatorial synthesis and the selection of new photodynamic therapeutic using a cancer cell line, J. Comb. Chem., 2007, 9, 998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. S. Hirohara, M. Obata, H. Alitomo, K. Sharyo, T. Ando, M. Tanihara and S. Yano, J. Photochem. Photobiol., 2009, 33, 9722.

    Google Scholar 

  44. A. M. G. Silva, A. C. Tomé, M. G. P. M. S. Neves, A. M. S. Silva and J. A. S. Cavaleiro, meso-Tetraarylporphyrins as dipolarophiles in 1,3-dipolar cycloaddition reactions, Chem. Commun., 1999, 1767.

    Google Scholar 

  45. S. Singh, A. Aggarwal, S. Thompson, J. P. C. Tomé, X. Zhu, D. Samaroo, M. Vinodu, R. Gao and C. M. Drain, Synthesis and photophysical properties of thioglycosylated chlorins, isobacteriochlorins, and bacteriochlorins for bioimaging and diagnostics, Bioconjugate Chem., 2010, 21, 2136.

    Article  CAS  Google Scholar 

  46. F. S. Vinhado, M. E. F. Gandini, Y. Iamamoto, A. M. G. Silva, M. M. Q. Simões, M. G. P. M. S. Neves, A. C. Tomé, S. L. H. Rebelo, A. M. V. M. Pereira and J. A. S. Cavaleiro, Novel Mn(iii) chlorins as versatile catalysts for oxyfunctionalisation of hydrocarbons under homogeneous conditions, J. Mol. Catal. A: Chem., 2005, 239, 138.

    Article  CAS  Google Scholar 

  47. E. Hao, E. Friso, G. Miotto, G. Jori, M. Soncin, C. Fabris, M. Sibrian-Vazqueza and M. G. H. Vicente, Synthesis and biological investigations of tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC), Org. Biomol. Chem., 2008, 6, 3732.

    Article  CAS  PubMed  Google Scholar 

  48. W. Spiller, H. Kliesch, D. Wöhrle, S. Hackbarth, B. Röder and G. Schnurpfeil, Singlet oxygen quantum yields of different photosensitizers in polar solvents and micellar solutions, J. Porphyrins Phthalocyanines, 1998, 2, 145.

    Article  CAS  Google Scholar 

  49. T. N. Demidova and M. R. Hamblin, Photodynamic inactivation of Bacillus spores, mediated by phenothiazinium dyes, Appl. Environ. Microbiol., 2005, 71, 6918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. T. Maisch, A new strategy to destroy antibiotic resistant microorganisms: antimicrobial photodynamic treatment, Mini-Rev. Med. Chem., 2009, 9, 974.

    Article  CAS  PubMed  Google Scholar 

  51. R. Bonnett, S. Ioannou, R. D. White, U. J. Winfield and M. C. Berenbaum, Photobiochem. Photobiophys., 1987, 45.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, QOPNA, University of Aveiro, Campus of Santiago, 3810-193, Aveiro, Portugal

    Dora C. S. Costa, Maria C. Gomes, Maria A. F. Faustino, Maria G. P. M. S. Neves, José A. S. Cavaleiro & João P. C. Tomé

  2. Department of Biology, CESAM, University of Aveiro, Campus of Santiago, 3810-193, Aveiro, Portugal

    Dora C. S. Costa, Maria C. Gomes, Ângela Cunha & Adelaide Almeida

Authors
  1. Dora C. S. Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria C. Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria A. F. Faustino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria G. P. M. S. Neves
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ângela Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José A. S. Cavaleiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adelaide Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. João P. C. Tomé
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Adelaide Almeida or João P. C. Tomé.

Additional information

Electronic supplementary information (ESI) available. See DOI: 10.1039/c2pp25113b

Rights and permissions

Reprints and permissions

About this article

Cite this article

Costa, D.C.S., Gomes, M.C., Faustino, M.A.F. et al. Comparative photodynamic inactivation of antibiotic resistant bacteria by first and second generation cationic photosensitizers. Photochem Photobiol Sci 11, 1905–1913 (2012). https://doi.org/10.1039/c2pp25113b

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c2pp25113b

Search

Navigation