AccScience Publishing / JCTR / Volume 1 / Issue 3 / DOI: 10.18053/jctres.201503.002
REVIEW

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

Yao Liu1*† Sebastian A. J. Zaat2 Eefjan Breukink1 Michal Heger1,3
Show Less
1 Department of Membrane Biochemistry and Biophysics, Utrecht University, the Netherlands
2 Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, the Netherlands
3 Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, the Netherlands
JCTR 2015, 1(3), 140–167; https://doi.org/10.18053/jctres.201503.002
Submitted: 5 November 2015 | Revised: 22 November 2015 | Published: 1 December 2015
© 2015 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Antibacterial photodynamic therapy (APDT) has drawn increasing attention from the scientific society for its potential to effectively kill multidrug-resistant pathogenic bacteria and for its low tendency to induce drug resistance that bacteria can rapidly develop against traditional antibiotic therapy. The review summarizes the mechanism of action of APDT, the photosensitizers, the barriers of PS localization, the targets, the in vitro, in vivo, and the clinical evidence, the current development against both Gram-positive and Gram-negative bacteria, the limitations, as well as some future perspectives.
Relevance for patients: A structured overview of all important aspects of APDT is provided in the context of resistant bacterial species. The information presented is relevant and accessible for scientists as well as clinicians, whose joint effort is required to ensure that this technology benefits patients in the post-antibiotic era.

Keywords
Antibacterial photodynamic therapy
bacterial cell envelope
photosensitizer
non-selectivity
reactive oxygen species
singlet oxygen
multidrug resistance
light dose
illumination
Conflict of interest
The authors declare they have no competing interests.
References

[1] Huang L, Xuan Y, Koide Y, Zhiyentayev T, Tanaka M, Hamblin MR. Type i and type ii mechanisms of antimicrobial photodynamic therapy: An in vitro study on gram-negative and gram- positive bacteria. Lasers Surg Med 2012; 44: 490-499.

[2] Reiniers MJ, van Golen RF, van Gulik TM, Heger M. Reactive oxygen and nitrogen species in steatotic hepatocytes: A molecular perspective on the pathophysiology of ischemia-reperfusion injury in the fatty liver. Antioxid Redox Signal 2014; 21: 1119-1142.

[3] van Golen RF, van Gulik TM, Heger M. Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury. Free Radic Biol Med 2012; 52: 1382-1402.

[4] Lauro FM, Pretto P, Covolo L, Jori G, Bertoloni G. Photoinactivation of bacterial strains involved in periodontal diseases sensitized by porphycene-polylysine conjugates. Photochem Photobiol Sci 2002; 1: 468-470.

[5] Schastak S, Ziganshyna S, Gitter B, Wiedemann P, Claudepierre T. Efficient photodynamic therapy against gram-positive and gram-negative bacteria using thpts, a cationic photosensitizer excited by infrared wavelength. PLoS One 2010; 5: e11674.

[6] Hamblin MR, Jori G. Photodynamic inactivation of microbial pathogens: Medical and environmental applications. Cambridge, UK, RSC Publishing, 2011.

[7] Tim M. Strategies to optimize photosensitizers for photodynamic inactivation of bacteria. J Photochem Photobiol B 2015

[8] Merchat M, Bertolini G, Giacomini P, Villanueva A, Jori G. Meso-substituted cationic porphyrins as efficient photosensitizers of gram-positive and gram-negative bacteria. J Photochem Photobiol B 1996; 32: 153-157.

[9] Minnock A, Vernon DI, Schofield J, Griffiths J, Parish JH, Brown ST. Photoinactivation of bacteria. Use of a cationic water-soluble zinc phthalocyanine to photoinactivate both gramnegative and gram-positive bacteria. J Photochem Photobiol B 1996; 32: 159-164.

[10] Wilson M, Burns T, Pratten J, Pearson GJ. Bacteria in supragingival plaque samples can be killed by low-power laser light in the presence of a photosensitizer. J Appl Bacteriol 1995; 78: 569-574.

[11] Mejlholm O, Dalgaard P. Modelling and predicting the simultaneous growth of listeria monocytogenes and psychrotolerant lactic acid bacteria in processed seafood and mayonnaise-based seafood salads. Food Microbiol 2015; 46: 1-14.

[12] Tome JP, Neves MG, Tome AC, Cavaleiro JA, Soncin M, Magaraggia M, Ferro S, Jori G. Synthesis and antibacterial activity of new poly-s-lysine-porphyrin conjugates. J Med Chem 2004; 47: 6649-6652.

[13] Maisch T, Hackbarth S, Regensburger J, Felgentrager A, Baumler W, Landthaler M, Roder B. Photodynamic inactivation of multi-resistant bacteria (pib) - a new approach to treat superficial infections in the 21st century. J Dtsch Dermatol Ges 2011; 9: 360-366.

[14] Tardivo JP, Del Giglio A, de Oliveira CS, Gabrielli DS, Junqueira HC, Tada DB, Severino D, de Fatima Turchiello R, Baptista MS. Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications. Photodiagnosis Photodyn Ther 2005; 2: 175-191.

[15] Vilela SF, Junqueira JC, Barbosa JO, Majewski M, Munin E, Jorge AO. Photodynamic inactivation of staphylococcus aureus and escherichia coli biofilms by malachite green and phenothiazine dyes: An in vitro study. Arch Oral Biol 2012; 57: 704-710.

[16] Viola G, Dall'Acqua F. Photosensitization of biomolecules by phenothiazine derivatives. Curr Drug Targets 2006; 7: 1135- 1154.

[17] Hussain S, Harris F, Phoenix DA. The phototoxicity of phenothiazinium-based photosensitizers to bacterial membranes. FEMS Immunol Med Microbiol 2006; 46: 124-130.

[18] Usacheva MN, Teichert MC, Biel MA. The interaction of lipopolysaccharides with phenothiazine dyes. Lasers Surg Med 2003; 33: 311-319.

[19] Felgentrager A, Maisch T, Dobler D, Spath A. Hydrogen bond acceptors and additional cationic charges in methylene blue derivatives: Photophysics and antimicrobial efficiency. Biomed Res Int 2013; 2013: 482167.

[20] Gollmer A, Felgentrager A, Baumler W, Maisch T, Spath A. A novel set of symmetric methylene blue derivatives exhibits effective bacteria photokilling-a structure-response study. Photochem Photobiol Sci 2015; 14: 335-351.

[21] Donnelly RF, Cassidy CM, Loughlin RG, Brown A, Tunney MM, Jenkins MG, McCarron PA. Delivery of methylene blue and meso-tetra (n-methyl-4-pyridyl) porphine tetra tosylate from cross-linked poly(vinyl alcohol) hydrogels: A potential means of photodynamic therapy of infected wounds. J Photochem Photobiol B 2009; 96: 223-231.

[22] Dai T, Huang YY, Hamblin MR. Photodynamic therapy for localized infections--state of the art. Photodiagnosis Photodyn Ther 2009; 6: 170-188.

[23] Soncin M, Fabris C, Busetti A, Dei D, Nistri D, Roncucci G, Jori G. Approaches to selectivity in the zn(ii)-phthalocyaninephotosensitized inactivation of wild-type and antibiotic-resistant staphylococcus aureus. Photochem Photobiol Sci 2002; 1: 815-819.

[24] Hamblin MR, Dai T. Can surgical site infections be treated by photodynamic therapy? Photodiagnosis Photodyn Ther 2010; 7: 134-136.

[25] Tegos GP, Hamblin MR. Phenothiazinium antimicrobial photosensitizers are substrates of bacterial multidrug resistance pumps. Antimicrob Agents Chemother 2006; 50: 196-203.

[26] Spengler G, Takacs D, Horvath A, Szabo AM, Riedl Z, Hajos G, Molnar J, Burian K. Efflux pump inhibiting properties of racemic phenothiazine derivatives and their enantiomers on the bacterial acrab-tolc system. In Vivo 2014; 28: 1071-1075.

[27] Tegos GP, Masago K, Aziz F, Higginbotham A, Stermitz FR, Hamblin MR. Inhibitors of bacterial multidrug efflux pumps potentiate antimicrobial photoinactivation. Antimicrob Agents Chemother 2008; 52: 3202-3209.

[28] Kishen A, Upadya M, Tegos GP, Hamblin MR. Efflux pump inhibitor potentiates antimicrobial photodynamic inactivation of enterococcus faecalis biofilm. Photochem Photobiol 2010; 86: 1343-1349.

[29] Wang Y, Venter H, Ma S. Efflux pump inhibitors: A novel approach to combat efflux-mediated drug resistance in bacteria. Curr Drug Targets 2015

[30] Huang L, St Denis TG, Xuan Y, Huang YY, Tanaka M, Zadlo A, Sarna T, Hamblin MR. Paradoxical potentiation of methylene blue-mediated antimicrobial photodynamic inactivation by sodium azide: Role of ambient oxygen and azide radicals. Free Radic Biol Med 2012; 53: 2062-2071.

[31] Kasimova KR, Sadasivam M, Landi G, Sarna T, Hamblin MR. Potentiation of photoinactivation of gram-positive and gramnegative bacteria mediated by six phenothiazinium dyes by addition of azide ion. Photochem Photobiol Sci 2014; 13: 1541- 1548.

[32] Weijer R, Broekgaarden M, Kos M, van Vught R, Rauws EA, Breukink E, van Gulik TM, Storm G, Heger M. Enhancing photodynamic therapy of refractory solid cancers: Combining second-generation photosensitizers with multi-targeted liposomal delivery. Journal of Photochemistry and Photobiology C: Photochemistry Reviews 2015

[33] Rothemund P. A new porphyrin synthesis. The synthesis of porphin1. Journal of the American Chemical Society 1936; 58: 625-627.

[34] Rothemund P. Formation of porphyrins from pyrrole and aldehydes. Journal of the American Chemical Society 1935; 57: 2010-2011.

[35] Tavares A, Dias SR, Carvalho CM, Faustino MA, Tome JP, Neves MG, Tome AC, Cavaleiro JA, Cunha A, Gomes NC, Alves E, Almeida A. Mechanisms of photodynamic inactivation of a gram-negative recombinant bioluminescent bacterium by cationic porphyrins. Photochem Photobiol Sci 2011; 10: 1659- 1669.

[36] Lambrechts SA, Aalders MC, Langeveld-Klerks DH, Khayali Y, Lagerberg JW. Effect of monovalent and divalent cations on the photoinactivation of bacteria with meso-substituted cationic porphyrins. Photochem Photobiol 2004; 79: 297-302.

[37] Alves E, Costa L, Carvalho CM, Tome JP, Faustino MA, Neves MG, Tome AC, Cavaleiro JA, Cunha A, Almeida A. Charge effect on the photoinactivation of gram-negative and grampositive bacteria by cationic meso-substituted porphyrins. BMC Microbiol 2009; 9: 70.

[38] Hanakova A, Bogdanova K, Tomankova K, Pizova K, Malohlava J, Binder S, Bajgar R, Langova K, Kolar M, Mosinger J, Kolarova H. The application of antimicrobial photodynamic therapy on s. Aureus and e. Coli using porphyrin photosensitizers bound to cyclodextrin. Microbiol Res 2014; 169: 163- 170.

[39] Prasanth CS, Karunakaran SC, Paul AK, Kussovski V, Mantareva V, Ramaiah D, Selvaraj L, Angelov I, Avramov L, Nandakumar K, Subhash N. Antimicrobial photodynamic efficiency of novel cationic porphyrins towards periodontal gram- positive and gram-negative pathogenic bacteria. Photochem Photobiol 2014; 90: 628-640.

[40] Alves E, Costa L, Carvalho CM, Tomé JP, Faustino MA, Neves MG, Tomé AC, Cavaleiro JA, Cunha Â, Almeida A. Charge effect on the photoinactivation of gram-negative and gram-positive bacteria by cationic meso-substituted porphyrins. BMC microbiology 2009; 9: 70.

[41] Caminos DA, Spesia MB, Pons P, Durantini EN. 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: 1071-1078.

[42] Dosselli R, Tampieri C, Ruiz-Gonzalez R, De Munari S, Ragas X, Sanchez-Garcia D, Agut M, Nonell S, Reddi E, Gobbo M. Synthesis, characterization, and photoinduced antibacterial activity of porphyrin-type photosensitizers conjugated to the antimicrobial peptide apidaecin 1b. J Med Chem 2013; 56: 1052-1063.

[43] Dosselli R, Gobbo M, Bolognini E, Campestrini S, Reddi E. Porphyrin-apidaecin conjugate as a new broad spectrum antibacterial agent. ACS Med Chem Lett 2010; 1: 35-38.

[44] Bourre L, Giuntini F, Eggleston IM, Mosse CA, Macrobert AJ, Wilson M. Effective photoinactivation of gram-positive and gram-negative bacterial strains using an hiv-1 tat peptide-porphyrin conjugate. Photochem Photobiol Sci 2010; 9: 1613- 1620.

[45] Dosselli R, Ruiz-Gonzalez R, Moret F, Agnolon V, Compagnin C, Mognato M, Sella V, Agut M, Nonell S, Gobbo M, Reddi E. Synthesis, spectroscopic, and photophysical characterization and photosensitizing activity toward prokaryotic and eukaryotic cells of porphyrin-magainin and -buforin conjugates. J Med Chem 2014; 57: 1403-1415.

[46] Kang SJ, Park SJ, Mishig-Ochir T, Lee BJ. Antimicrobial peptides: Therapeutic potentials. Expert Rev Anti Infect Ther 2014; 12: 1477-1486.

[47] Kessel D, Luguya R, Vicente MG. Localization and photodynamic efficacy of two cationic porphyrins varying in charge distributions. Photochem Photobiol 2003; 78: 431-435.

[48] Bertoloni G, Rossi F, Valduga G, Jori G, van Lier J. Photosensitizing activity of water- and lipid-soluble phthalocyanines on escherichia coli. FEMS Microbiol Lett 1990; 59: 149-155.

[49] Bertoloni G, Rossi F, Valduga G, Jori G, Ali H, van Lier JE. Photosensitizing activity of water- and lipid-soluble phthalocyanines on prokaryotic and eukaryotic microbial cells. Microbios 1992; 71: 33-46.

[50] Minnock A, Vernon DI, Schofield J, Griffiths J, Parish JH, Brown SB. Mechanism of uptake of a cationic water-soluble pyridinium zinc phthalocyanine across the outer membrane of escherichia coli. Antimicrob Agents Chemother 2000; 44: 522-527.

[51] Spesia MB, Caminos DA, Pons P, Durantini EN. Mechanistic insight of the photodynamic inactivation of Escherichia coli by a tetracationic zinc(ii) phthalocyanine derivative. Photodiagnosis Photodyn Ther 2009; 6: 52-61.

[52] Strakhovskaya MG, Antonenko YN, Pashkovskaya AA, Kotova EA, Kireev V, Zhukhovitsky VG, Kuznetsova NA, Yuzhakova OA, Negrimovsky VM, Rubin AB. Electrostatic binding of substituted metal phthalocyanines to enterobacterial cells: Its role in photodynamic inactivation. Biochemistry (Mosc) 2009; 74: 1305-1314.

[53] Spesia MB, Rovera M, Durantini EN. Photodynamic inactivation of escherichia coli and streptococcus mitis by cationic zinc(ii) phthalocyanines in media with blood derivatives. Eur J Med Chem 2010; 45: 2198-2205.

[54] Spesia MB, Durantini EN. Photodynamic inactivation mechanism of streptococcus mitis sensitized by zinc(ii) 2, 9, 16, 23-tetrakis[2-(n, n, n-trimethylamino)ethoxy]phthalocyanine. J Photochem Photobiol B 2013; 125: 179-187.

[55] Giuliani F, Martinelli M, Cocchi A, Arbia D, Fantetti L, Roncucci G. In vitro resistance selection studies of rlp068/cl, a new zn(ii) phthalocyanine suitable for antimicrobial photodynamic therapy. Antimicrob Agents Chemother 2010; 54: 637-642.

[56] Scalise I, Durantini EN. Synthesis, properties, and photodynamic inactivation of escherichia coli using a cationic and a noncharged zn(ii) pyridyloxyphthalocyanine derivatives. Bioorg Med Chem 2005; 13: 3037-3045.

[57] Ke MR, Eastel JM, Ngai KL, Cheung YY, Chan PK, Hui M, Ng DK, Lo PC. Photodynamic inactivation of bacteria and viruses using two monosubstituted zinc(ii) phthalocyanines. Eur J Med Chem 2014; 84: 278-283.

[58] Mikula P, Kalhotka L, Jancula D, Zezulka S, Korinkova R, Cerny J, Marsalek B, Toman P. Evaluation of antibacterial properties of novel phthalocyanines against escherichia coli-- comparison of analytical methods. J Photochem Photobiol B 2014; 138: 230-239.

[59] Tegos GP, Demidova TN, Arcila-Lopez D, Lee H, Wharton T, Gali H, Hamblin MR. Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chem Biol 2005; 12: 1127-1135.

[60] Huang L, Wang M, Dai T, Sperandio FF, Huang YY, Xuan Y, Chiang LY, Hamblin MR. Antimicrobial photodynamic therapy with decacationic monoadducts and bisadducts of [70]fullerene: In vitro and in vivo studies. Nanomedicine (Lond) 2014; 9: 253-266.

[61] Kato T, Kodama T, Shida T, Nakagawa T, Matsui Y, Suzuki S, Shiromaru H, Yamauchi K, Achiba Y. Electronic absorption spectra of the radical anions and cations of fullerenes: C 60 and c 70. Chem Phys Lett 1991; 180: 446-450.

[62] Ballatore MB, Durantini J, Gsponer NS, Suarez MB, Gervaldo M, Otero L, Spesia MB, Milanesio ME, Durantini EN. Photodynamic inactivation of bacteria using novel electrogenerated porphyrin-fullerene c60 polymeric films. Environ Sci Technol 2015; 49: 7456-7463.

[63] Ballatore MB, Spesia MB, Milanesio ME, Durantini EN. Synthesis, spectroscopic properties and photodynamic activity of porphyrin-fullerene c60 dyads with application in the photodynamic inactivation of staphylococcus aureus. Eur J Med Chem 2014; 83: 685-694.

[64] Huang YY, Sharma SK, Yin R, Agrawal T, Chiang LY, Hamblin MR. Functionalized fullerenes in photodynamic therapy. J Biomed Nanotechnol 2014; 10: 1918-1936.

[65] Arbogast JW, Foote CS, Kao M. Electron transfer to triplet fullerene c60. J Am Chem Soc 1992; 114: 2277-2279.

[66] Guldi DM, Prato M. Excited-state properties of c60 fullerene derivatives. Accounts of chemical research 2000; 33: 695-703.

[67] Guldi DM, Maggini M, Scorrano G, Prato M. Intramolecular electron transfer in fullerene/ferrocene based donor-bridge-acceptor dyads. J Am Chem Soc 1997; 119: 974-980.

[68] Nojiri T, Alam MM, Konami H, Watanabe A, Ito O. Photoinduced electron transfer from phthalocyanines to fullerenes (c60 and c70). J Phys Chem A 1997; 101: 7943-7947.

[69] Gottschalk G. Bacterial metabolism. Springer Science & Business Media, 2012.

[70] Bock E, Schmidt I, Stüven R, Zart D. Nitrogen loss caused by denitrifying nitrosomonas cells using ammonium or hydrogen as electron donors and nitrite as electron acceptor. Arch Microbiol 1995; 163: 16-20.

[71] Hooper AB, Vannelli T, Bergmann DJ, Arciero DM. Enzymology of the oxidation of ammonia to nitrite by bacteria. Antonie van Leeuwenhoek 1997; 71: 59-67.

[72] Widdel F, Pfennig N. A new anaerobic, sporing, acetate-oxidizing, sulfate-reducing bacterium, desulfotomaculum (emend.) acetoxidans. Arch Microbiol 1977; 112: 119-122.

[73] Widdel F, Schnell S, Heising S, Ehrenreich A, Assmus B, Schink B. Ferrous iron oxidation by anoxygenic phototrophic bacteria. Nature 1993; 362: 834-836.

[74] Spesia MB, Milanesio ME, Durantini EN. Synthesis, properties and photodynamic inactivation of escherichia coli by novel cationic fullerene c60 derivatives. Eur J Med Chem 2008; 43: 853-861.

[75] Culotta L, Koshland DE, Jr.. Buckyballs. Wide open playing field for chemists. Science 1991; 254: 1706-1709.

[76] Zhang Y, Dai T, Wang M, Vecchio D, Chiang LY, Hamblin MR. Potentiation of antimicrobial photodynamic inactivation medi-ated by a cationic fullerene by added iodide: in vitro and in vivo studies. Nanomedicine (Lond) 2015; 10: 603-614.

[77] Yin R, Wang M, Huang YY, Landi G, Vecchio D, Chiang LY, Hamblin MR. Antimicrobial photodynamic inactivation with decacationic functionalized fullerenes: Oxygen-independent photokilling in presence of azide and new mechanistic insights. Free Radic Biol Med 2015; 79: 14-27.

[78] Lavie G, Mazur Y, Lavie D, Prince A, Pascual D, Liebes L, Levin B, Meruelo D. Hypericin as an inactivator of infectious viruses in blood components. Transfusion 1995; 35: 392-400.

[79] Stevenson NR, Lenard J. Antiretroviral activities of hypericin and rose bengal: Photodynamic effects on friend leukemia virus infection of mice. Antiviral Res 1993; 21: 119-127.

[80] Garcia I, Ballesta S, Gilaberte Y, Rezusta A, Pascual A. Antimicrobial photodynamic activity of hypericin against methicillin-susceptible and resistant staphylococcus aureus biofilms. Future Microbiol 2015; 10: 347-356.

[81] Engelhardt V, Krammer B, Plaetzer K. Antibacterial photodynamic therapy using water-soluble formulations of hypericin or mthpc is effective in inactivation of staphylococcus aureus. Photochem Photobiol Sci 2010; 9: 365-369.

[82] Kashef N, Karami S, Djavid GE. Phototoxic effect of hypericin alone and in combination with acetylcysteine on staphylococcus aureus biofilms. Photodiagnosis Photodyn Ther 2015; 12: 186-192.

[83] Yow CM, Tang HM, Chu ES, Huang Z. Hypericin-mediated photodynamic antimicrobial effect on clinically isolated pathogens. Photochem Photobiol 2012; 88: 626-632.

[84] Souza MI, Silva ER, Jaques YM, Ferreira FF, Fileti EE, Alves WA. The role of water and structure on the generation of reactive oxygen species in peptide/hypericin complexes. J Pept Sci 2014; 20: 554-562.

[85] Gad F, Zahra T, Hasan T, Hamblin MR. Effects of growth phase and extracellular slime on photodynamic inactivation of gram-positive pathogenic bacteria. Antimicrob Agents Chemother 2004; 48: 2173-2178.

[86] Dinicola S, De Grazia S, Carlomagno G, Pintucci JP. N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med Pharmacol Sci 2014; 18: 2942-2948.

[87] Aslam S, Darouiche RO. Role of antibiofilm-antimicrobial agents in controlling device-related infections. Int J Artif Organs 2011; 34: 752-758.

[88] Masip L, Veeravalli K, Georgiou G. The many faces of glutathione in bacteria. Antioxid Redox Signal 2006; 8: 753-762.

[89] Goswami M, Jawali N. N-acetylcysteine-mediated modulation of bacterial antibiotic susceptibility. Antimicrob Agents Chemother 2010; 54: 3529-3530.

[90] Smirnova GV, Oktyabrsky ON. Glutathione in bacteria. Biochemistry (Mosc) 2005; 70: 1199-1211.

[91] Tonon CC, Paschoal MA, Correia M, Spolidorio DM, Bagnato VS, Giusti JS, Santos-Pinto L. Comparative effects of photodynamic therapy mediated by curcumin on standard and clinical isolate of Streptococcus mutans. J Comtemp Det Pract. 2015; 1: 1-6.

[92] Winter S, Tortik N, Kubin A, Krammer B, Plaetzer K. Back to the roots: photodynamic inactivation of bacteria based on water-soluble curcumin bound to polyvinylpyrrolidone as a photosensitizer. Photochem Photobiol Sci 2013; 12: 1795-1802.

[93] Araujo NC, Fontana CR, Bagnato VS, Gerbi ME. Photodynamic antimicrobial therapy of curcumin in biofilms and carious dentine. Lasers Med Sci 2014; 29: 629-635.

[94] Heger M, van Golen RF, Broekgaarden M, Michel MC. The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacol Rev 2014; 66: 222-307.

[95] Dahl TA, McGowan WM, Shand MA, Srinivasan VS. Photokilling of bacteria by the natural dye curcumin. Arch Microbiol 1989; 151: 183-185.

[96] Dahl TA, Bilski P, Reszka KJ, Chignell CF. Photocytotoxicity of curcumin. Photochem Photobiol 1994; 59: 290-294.

[97] Mucsi Z, Chass GA, Abranyi-Balogh P, Jojart B, Fang DC, Ramirez-Cuesta AJ, Viskolcz B, Csizmadia IG. Penicillin's catalytic mechanism revealed by inelastic neutrons and quantum chemical theory. Phys Chem Chem Phys 2013; 15: 20447- 20455.

[98] Horliana RF, Horliana AC, Wuo Ado V, Perez FE, Abrao J. Dental extrusion with orthodontic miniscrew anchorage: A case report describing a modified method. Case Rep Dent 2015; 2015: 909314.

[99] Tally FP, DeBruin MF. Development of daptomycin for grampositive infections. J Antimicrob Chemother 2000; 46: 523-526.

[100] Alves E, Faustino MA, Neves MG, Cunha A, Tome J, Almeida A. An insight on bacterial cellular targets of photodynamic inactivation. Future Med Chem 2014; 6: 141-164.

[101] Silhavy TJ, Kahne D, Walker S. The bacterial cell envelope. Cold Spring Harb Perspect Biol 2010; 2: a000414.

[102] Hamblin MR, O'Donnell DA, Murthy N, Rajagopalan K, Michaud N, Sherwood ME, Hasan T. Polycationic photosensitizer conjugates: Effects of chain length and gram classification on the photodynamic inactivation of bacteria. J Antimicrob Chemother 2002; 49: 941-951.

[103] Demidova TN, Hamblin MR. Effect of cell-photosensitizer binding and cell density on microbial photoinactivation. Antimicrob Agents Chemother 2005; 49: 2329-2335.

[104] Anwar MA, Choi S. Gram-negative marine bacteria: Structural features of lipopolysaccharides and their relevance for economically important diseases. Mar Drugs 2014; 12: 2485-2514.

[105] Freudenberg MA, Tchaptchet S, Keck S, Fejer G, Huber M, Schutze N, Beutler B, Galanos C. Lipopolysaccharide sensing an important factor in the innate immune response to gram-negative bacterial infections: Benefits and hazards of lps hypersensitivity. Immunobiology 2008; 213: 193-203.

[106] Freudenberg MA, Merlin T, Gumenscheimer M, Kalis C, Landmann R, Galanos C. Role of lipopolysaccharide susceptibility in the innate immune response to salmonella typhimurium infection: Lps, a primary target for recognition of gramnegative bacteria. Microbes Infect 2001; 3: 1213-1222.

[107] Shrestha A, Cordova M, Kishen A. Photoactivated polycationic bioactive chitosan nanoparticles inactivate bacterial endotoxins.J Endod 2015; 41: 686-691.

[108] George S, Hamblin MR, Kishen A. Uptake pathways of anionic and cationic photosensitizers into bacteria. Photochem Photobiol Sci 2009; 8: 788-795.

[109] Bemporad D, Luttmann C, Essex JW. Computer simulation of small molecule permeation across a lipid bilayer: dependence on bilayer properties and solute volume, size, and cross-sectional area. Biophys J 2004; 87: 1-13.

[110] Fernandez L, Hancock RE. Adaptive and mutational resistance: Role of porins and efflux pumps in drug resistance. Clin Microbiol Rev 2012; 25: 661-681.

[111] Galdiero S, Falanga A, Cantisani M, Tarallo R, Della Pepa ME, D'Oriano V, Galdiero M. Microbe-host interactions: Structure and role of gram-negative bacterial porins. Curr Protein Pept Sci 2012; 13: 843-854.

[112] Brown S, Santa Maria JP, Jr., Walker S. Wall teichoic acids of gram-positive bacteria. Annu Rev Microbiol 2013; 67: 313- 336.

[113] Demchick P, Koch AL. The permeability of the wall fabric of escherichia coli and bacillus subtilis. J Bacteriol 1996; 178: 768-773.

[114] Pereira MA, Faustino MA, Tome JP, Neves MG, Tome AC, Cavaleiro JA, Cunha A, Almeida A. Influence of external bacterial structures on the efficiency of photodynamic inactivation by a cationic porphyrin. Photochem Photobiol Sci 2014; 13: 680-690.

[115] Zhang YM, Rock CO. Membrane lipid homeostasis in bacteria. Nat Rev Microbiol 2008; 6: 222-233.

[116] Barak I, Muchova K. The role of lipid domains in bacterial cell processes. Int J Mol Sci 2013; 14: 4050-4065.

[117] Epand RM, Epand RF. Lipid domains in bacterial membranes and the action of antimicrobial agents. Biochim Biophys Acta 2009; 1788: 289-294.

[118] Rice LB. Antimicrobial resistance in gram-positive bacteria. Am J Med 2006; 119: S11-19; discussion S62-70.

[119] Cabiscol E, Tamarit J, Ros J. Oxidative stress in bacteria and protein damage by reactive oxygen species. Int Microbiol 2000; 3: 3-8.

[120] Lopes D, Melo T, Santos N, Rosa L, Alves E, Clara Gomes M, Cunha A, Neves MG, Faustino MA, Domingues MR, Almeida A. Evaluation of the interplay among the charge of porphyrinic photosensitizers, lipid oxidation and photoinactivation efficiency in escherichia coli. J Photochem Photobiol B 2014; 141: 145-153.

[121] Alves E, Santos N, Melo T, Maciel E, Doria ML, Faustino MA, Tome JP, Neves MG, Cavaleiro JA, Cunha A, Helguero LA, Domingues P, Almeida A, Domingues MR. Photodynamic oxidation of escherichia coli membrane phospholipids: New insights based on lipidomics. Rapid Commun Mass Spectrom 2013; 27: 2717-2728.

[122] Laganowsky A, Reading E, Allison TM, Ulmschneider MB, Degiacomi MT, Baldwin AJ, Robinson CV. Membrane proteins bind lipids selectively to modulate their structure and function. Nature 2014; 510: 172-175.

[123] Johnson GA, Ellis EA, Kim H, Muthukrishnan N, Snavely T, Pellois JP. Photoinduced membrane damage of e. Coli and s. Aureus by the photosensitizer-antimicrobial peptide conjugate eosin-(klaklak)2. PLoS One 2014; 9: e91220.

[124] Preuss A, Zeugner L, Hackbarth S, Faustino MA, Neves MG, Cavaleiro JA, Roeder B. Photoinactivation of escherichia coli (sure2) without intracellular uptake of the photosensitizer. J Appl Microbiol 2013; 114: 36-43.

[125] Ragas X, Agut M, Nonell S. Singlet oxygen in escherichia coli: New insights for antimicrobial photodynamic therapy. Free Radic Biol Med 2010; 49: 770-776.

[126] Ragas X, He X, Agut M, Roxo-Rosa M, Gonsalves AR, Serra AC, Nonell S. Singlet oxygen in antimicrobial photodynamic therapy: Photosensitizer-dependent production and decay in e. Coli. Molecules 2013; 18: 2712-2725.

[127] Alves E, Faustino MA, Tome JP, Neves MG, Tome AC, Cavaleiro JA, Cunha A, Gomes NC, Almeida A. Nucleic acid changes during photodynamic inactivation of bacteria by cationic porphyrins. Bioorg Med Chem 2013; 21: 4311-4318.

[128] Salmon-Divon M, Nitzan Y, Malik Z. Mechanistic aspects of escherichia coli photodynamic inactivation by cationic tetrameso(n-methylpyridyl)porphine. Photochem Photobiol Sci 2004; 3: 423-429.

[129] Nitzan Y, Ashkenazi H. Photoinactivation of acinetobacter baumannii and escherichia coli b by a cationic hydrophilic porphyrin at various light wavelengths. Curr Microbiol 2001; 42: 408- 414.

[130] Nir U, Ladan H, Malik Z, Nitzan Y. In vivo effects of porphyrins on bacterial DNA. J Photochem Photobiol B 1991; 11: 295- 306.

[131] Dosselli R, Millioni R, Puricelli L, Tessari P, Arrigoni G, Franchin C, Segalla A, Teardo E, Reddi E. Molecular targets of antimicrobial photodynamic therapy identified by a proteomic approach. J Proteomics 2012; 77: 329-343.

[132] Menezes S, Capella MA, Caldas LR. Photodynamic action of methylene blue: Repair and mutation in escherichia coli. J Photochem Photobiol B 1990; 5: 505-517.

[133] Typas A, Sourjik V. Bacterial protein networks: Properties and functions. Nat Rev Microbiol 2015; 13: 559-572.

[134] Alves E, Esteves AC, Correia A, Cunha A, Faustino MA, Neves MG, Almeida A. Protein profiles of escherichia coli and staphylococcus warneri are altered by photosensitization with cationic porphyrins. Photochem Photobiol Sci 2015; 14: 1169- 1178.

[135] Visick JE, Clarke S. Repair, refold, recycle: How bacteria can deal with spontaneous and environmental damage to proteins. Mol Microbiol 1995; 16: 835-845.

[136] Broekgaarden M, Weijer R, van Gulik TM, Hamblin MR, Heger M. Tumor cell survival pathways activated by photodynamic therapy: A molecular basis for pharmacological inhibition strategies. Cancer Metastasis Rev 2015

[137] de Kievit TR. Quorum sensing in pseudomonas aeruginosa biofilms. Environ Microbiol 2009; 11: 279-288.

[138] Tseng SP, Teng LJ, Chen CT, Lo TH, Hung WC, Chen HJ, Hsueh PR, Tsai JC. Toluidine blue o photodynamic inactivation on multidrug-resistant pseudomonas aeruginosa. Lasers Surg Med 2009; 41: 391-397.

[139] Lee CF, Lee CJ, Chen CT, Huang CT. Delta-aminolaevulinic acid mediated photodynamic antimicrobial chemotherapy on pseudomonas aeruginosa planktonic and biofilm cultures. J Photochem Photobiol B 2004; 75: 21-25.

[140] Hsieh C-M, Huang Y-H, Chen C-P, Hsieh B-C, Tsai T. 5-aminolevulinic acid induced photodynamic inactivation on staphylococcus aureus and pseudomonas aeruginosa. J Food Drug Anal 2014; 22: 350-355.

[141] Wilson M, Pratten J. Lethal photosensitisation of staphylococcus aureus in vitro: Effect of growth phase, serum, and pre-irradiation time. Lasers Surg Med 1995; 16: 272-276.

[142] Hajim KI, Salih DS, Rassam YZ. Laser light combined with a photosensitizer may eliminate methicillin-resistant strains of staphylococcus aureus. Lasers Med Sci 2010; 25: 743-748.

[143] Griffiths MA, Wren BW, Wilson M. Killing of methicillin-resistant staphylococcus aureus in vitro using aluminium disulphonated phthalocyanine, a light-activated antimicrobial agent. J Antimicrob Chemother 1997; 40: 873-876.

[144] Fu XJ, Fang Y, Yao M. Antimicrobial photodynamic therapy for methicillin-resistant staphylococcus aureus infection. Biomed Res Int 2013; 2013: 159157.

[145] Zheng X, Sallum UW, Verma S, Athar H, Evans CL, Hasan T. Exploiting a bacterial drug-resistance mechanism: A light-activated construct for the destruction of mrsa. Angew Chem Int Ed Engl 2009; 48: 2148-2151.

[146] Dos Santos Fernandes GF, Jornada DH, de Souza PC, Chin CM, Pavan FR, Dos Santos JL. Current advances in antitubercular drug discovery: Potent prototypes and new targets. Curr Med Chem 2015

[147] Bailo R, Bhatt A, Ainsa JA. Lipid transport in mycobacterium tuberculosis and its implications in virulence and drug development. Biochem Pharmacol 2015; 96: 159-167.

[148] Daffe M, Etienne G. The capsule of mycobacterium tuberculosis and its implications for pathogenicity. Tuber Lung Dis 1999; 79: 153-169.

[149] Jackson M, McNeil MR, Brennan PJ. Progress in targeting cell envelope biogenesis in mycobacterium tuberculosis. Future Microbiol 2013; 8: 855-875.

[150] Moller KI, Kongshoj B, Philipsen PA, Thomsen VO, Wulf HC. How finsen's light cured lupus vulgaris. Photodermatol Photoimmunol Photomed 2005; 21: 118-124.

[151] Sung N, Back S, Jung J, Kim KH, Kim JK, Lee JH, Ra Y, Yang HC, Lim C, Cho S, Kim K, Jheon S. Inactivation of multidrug resistant (mdr)- and extensively drug resistant (xdr)-mycobacterium tuberculosis by photodynamic therapy. Photodiagnosis Photodyn Ther 2013; 10: 694-702.

[152] Yang Y, Auguin D, Delbecq S, Dumas E, Molle G, Molle V, Roumestand C, Saint N. Structure of the mycobacterium tuberculosis ompatb protein: A model of an oligomeric channel in the mycobacterial cell wall. Proteins 2011; 79: 645-661.

[153] Siroy A, Mailaender C, Harder D, Koerber S, Wolschendorf F, Danilchanka O, Wang Y, Heinz C, Niederweis M. Rv1698 of mycobacterium tuberculosis represents a new class of channel-forming outer membrane proteins. J Biol Chem 2008; 283: 17827-17837.

[154] Song H, Niederweis M. Uptake of sulfate but not phosphate by mycobacterium tuberculosis is slower than that for mycobacterium smegmatis. J Bacteriol 2012; 194: 956-964.

[155] Kartmann B, Stenger S, Niederweis M. Porins in the cell wall of mycobacterium tuberculosis. J Bacteriol 1999; 181: 6543- 6546.

[156] Feese E, Ghiladi RA. Highly efficient in vitro photodynamic inactivation of mycobacterium smegmatis. J Antimicrob Chemother 2009; 64: 782-785.

[157] O'Riordan K, Sharlin DS, Gross J, Chang S, Errabelli D, Akilov OE, Kosaka S, Nau GJ, Hasan T. Photoinactivation of mycobacteria in vitro and in a new murine model of localized mycobacterium bovis bcg-induced granulomatous infection. Antimicrob Agents Chemother 2006; 50: 1828-1834.

[158] Bruce-Micah R, Huttenberger D, Freitag L, Cullum J, Foth HJ. Pharmacokinetic of ala and h-ala induced porphyrins in the models mycobacterium phlei and mycobacterium smegmatis. J Photochem Photobiol B 2009; 97: 1-7.

[159] Rudys R, Denkovskij J, Kirdaite G, Bagdonas S. Induction of protoporphyrin ix in patient-derived synoviocytes, cartilage explants and chondrons after application of 5-aminolevulinic acid or its methyl ester. J Photochem Photobiol B 2014; 141: 228-234.

[160] Loesche WJ. Microbiology of dental decay and periodontal disease; in Baron S (ed): Medical microbiology. Galveston (TX), 1996

[161] Krzysciak W, Jurczak A, Koscielniak D, Bystrowska B, Skalniak A. The virulence of streptococcus mutans and the ability to form biofilms. Eur J Clin Microbiol Infect Dis 2014; 33: 499-515.

[162] Spath A, Leibl C, Cieplik F, Lehner K, Regensburger J, Hiller KA, Baumler W, Schmalz G, Maisch T. Improving photodynamic inactivation of bacteria in dentistry: Highly effective and fast killing of oral key pathogens with novel tooth- colored type-ii photosensitizers. J Med Chem 2014; 57: 5157-5168.

[163] Musk DJ, Jr., Hergenrother PJ. Chemical countermeasures for the control of bacterial biofilms: Effective compounds and promising targets. Curr Med Chem 2006; 13: 2163-2177.

[164] Susila AV, Sugumar R, Chandana CS, Subbarao CV. Combined effects of photodynamic therapy and irrigants in disinfection of root canals. J Biophotonics 2015

[165] Miyatani F, Kuriyama N, Watanabe I, Nomura R, Nakano K, Matsui D, Ozaki E, Koyama T, Nishigaki M, Yamamoto T, Mizuno T, Tamura A, Akazawa K, Takada A, Takeda K, Yamada K, Nakagawa M, Ihara M, Kanamura N, Friedland RP, Watanabe Y. Relationship between cnm-positive streptococcus mutans and cerebral microbleeds in humans. Oral Dis 2015; 21: 886-893.

[166] Nakano K, Inaba H, Nomura R, Nemoto H, Takeda M, Yoshioka H, Matsue H, Takahashi T, Taniguchi K, Amano A, Ooshima T. Detection of cariogenic streptococcus mutans in extirpated heart valve and atheromatous plaque specimens. J Clin Microbiol 2006; 44: 3313-3317.

[167] Pereira CA, Costa AC, Carreira CM, Junqueira JC, Jorge AO.Photodynamic inactivation of streptococcus mutans and streptococcus sanguinis biofilms in vitro. Lasers Med Sci 2013; 28: 859-864.

[168] Allaker RP, Douglas CW. Novel anti-microbial therapies for dental plaque-related diseases. Int J Antimicrob Agents 2009; 33: 8-13.

[169] Zanin IC, Goncalves RB, Junior AB, Hope CK, Pratten J. Susceptibility of streptococcus mutans biofilms to photodynamic therapy: An in vitro study. J Antimicrob Chemother 2005; 56: 324-330.

[170] Pandit S, Kim HJ, Kim JE, Jeon JG. Separation of an effective fraction from turmeric against streptococcus mutans biofilms by the comparison of curcuminoid content and anti-acidogenic activity. Food Chem 2011; 126: 1565-1570.

[171] Dahlen G, Samuelsson W, Molander A, Reit C. Identification and antimicrobial susceptibility of enterococci isolated from the root canal. Oral Microbiol Immunol 2000; 15: 309-312.

[172] Yilmaz N, Emmungil H, Gucenmez S, Ozen G, Yildiz F, Balkarli A, Kimyon G, Coskun BN, Dogan I, Pamuk ON, Yasar S, Cetin GY, Yazici A, Ergulu Esmen S, Cagatay Y, Yilmaz S, Cefle A, Sayarlioglu M, Kasifoglu T, Karadag O, Pehlivan Y, Dalkilic E, Kisacik B, Cobankara V, Erken E, Direskeneli H, Aksu K, Yavuz S. Incidence of cyclophosphamide-induced urotoxicity and protective effect of mesna in rheumatic diseases. J Rheumatol 2015; 42: 1661-1666.

[173] Foschi F, Fontana CR, Ruggiero K, Riahi R, Vera A, Doukas AG, Pagonis TC, Kent R, Stashenko PP, Soukos NS. Photodynamic inactivation of enterococcus faecalis in dental root canals in vitro. Lasers Surg Med 2007; 39: 782-787.

[174] Cieplik F, Spath A, Regensburger J, Gollmer A, Tabenski L, Hiller KA, Baumler W, Maisch T, Schmalz G. Photodynamic biofilm inactivation by sapyr--an exclusive singlet oxygen photosensitizer. Free Radic Biol Med 2013; 65: 477-487.

[175] Cieplik F, Pummer A, Regensburger J, Hiller KA, Spath A, Tabenski L, Buchalla W, Maisch T. The impact of absorbed photons on antimicrobial photodynamic efficacy. Front Microbiol 2015; 6: 706.

[176] Rimbara E, Fischbach LA, Graham DY. Optimal therapy for helicobacter pylori infections. Nat Rev Gastroenterol Hepatol 2011; 8: 79-88.

[177] Lim HC, Lee YJ, An B, Lee SW, Lee YC, Moon BS. Rifabutin-based high-dose proton-pump inhibitor and amoxicillin triple regimen as the rescue treatment for helicobacter pylori. Helicobacter 2014; 19: 455-461.

[178] Ontsira Ngoyi EN, Atipo Ibara BI, Moyen R, Ahoui Apendi PC, Ibara JR, Obengui O, Ossibi Ibara RB, Nguimbi E, Niama RF, Ouamba JM, Yala F, Abena AA, Vadivelu J, Goh KL, Menard A, Benejat L, Sifre E, Lehours P, Megraud F. Molecular detection of helicobacter pylori and its antimicrobial resistance in brazzaville, congo. Helicobacter 2015; 20: 316-320.

[179] Rasheed F, Campbell BJ, Alfizah H, Varro A, Zahra R, Yamaoka Y, Pritchard DM. Analysis of clinical isolates of helicobacter pylori in pakistan reveals high degrees of pathogenicity and high frequencies of antibiotic resistance. Helicobacter 2014; 19: 387-399.

[180] Zhang YX, Zhou LY, Song ZQ, Zhang JZ, He LH, Ding Y. Primary antibiotic resistance of helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: a prospective serial study. World J Gastroenterol 2015; 21: 2786-2792.

[181] Okamura T, Suga T, Nagaya T, Arakura N, Matsumoto T, Nakayama Y, Tanaka E. Antimicrobial resistance and characteristics of eradication therapy of helicobacter pylori in japan: A multi-generational comparison. Helicobacter 2014; 19: 214- 220.

[182] Roma E, Miele E. Helicobacter pylori infection in pediatrics. Helicobacter 2015; 20 Suppl 1: 47-53.

[183] Hamblin MR, Hasan T. Photodynamic therapy: A new antimicrobial approach to infectious disease? Photochem Photobiol Sci 2004; 3: 436-450.

[184] Calvino-Fernandez M, Garcia-Fresnadillo D, Benito-Martinez S, McNicholl AG, Calvet X, Gisbert JP, Parra-Cid T. Helicobacter pylori inactivation and virulence gene damage using a supported sensitiser for photodynamic therapy. Eur J Med Chem 2013; 68: 284-290.

[185] Hamblin MR, Viveiros J, Yang C, Ahmadi A, Ganz RA, Tolkoff MJ. Helicobacter pylori accumulates photoactive porphyrins and is killed by visible light. Antimicrob Agents Chemother 2005; 49: 2822-2827.

[186] Ganz RA, Viveiros J, Ahmad A, Ahmadi A, Khalil A, Tolkoff MJ, Nishioka NS, Hamblin MR. Helicobacter pylori in patients can be killed by visible light. Lasers Surg Med 2005; 36: 260- 265.

[187] Huang L, Huang YY, Mroz P, Tegos GP, Zhiyentayev T, Sharma SK, Lu Z, Balasubramanian T, Krayer M, Ruzie C, Yang E, Kee HL, Kirmaier C, Diers JR, Bocian DF, Holten D, Lindsey JS, Hamblin MR. Stable synthetic cationic bacteriochlorins as selective antimicrobial photosensitizers. Antimicrob Agents Chemother 2010; 54: 3834-3841.

[188] Vecchio D, Bhayana B, Huang L, Carrasco E, Evans CL, Hamblin MR. Structure-function relationships of nile blue (etnbs) derivatives as antimicrobial photosensitizers. Eur J Med Chem 2014; 75: 479-491.

[189] Dai T, Tegos GP, Lu Z, Huang L, Zhiyentayev T, Franklin MJ, Baer DG, Hamblin MR. Photodynamic therapy for acinetobacter baumannii burn infections in mice. Antimicrob Agents Chemother 2009; 53: 3929-3934.

[190] Wagner SJ, Skripchenko A, Donnelly DJ, Ramaswamy K, Detty MR. Chalcogenoxanthylium photosensitizers for the photodynamic purging of blood-borne viral and bacterial pathogens. Bioorg Med Chem 2005; 13: 5927-5935.

[191] Chen C, Chen C, Yang J, Tsai T. Liposome-encapsulated photosensitizers against bacteria. Recent Pat Antiinfect Drug Discov 2013; 8: 100-107.

[192] Ferro S, Ricchelli F, Monti D, Mancini G, Jori G. Efficient photoinactivation of methicillin-resistant staphylococcus aureus by a novel porphyrin incorporated into a poly-cationic liposome. Int J Biochem Cell Biol 2007; 39: 1026-1034.

[193] Ko A, Yee M, Skupin-Mrugalska P, Duzgunes N. Photodynamic therapy of porphyromonas gingivalis via liposome-encapsulated sensitizers. J Calif Dent Assoc 2013; 41: 827-830.

[194] Tsai T, Yang YT, Wang TH, Chien HF, Chen CT. Improved photodynamic inactivation of gram-positive bacteria using hematoporphyrin encapsulated in liposomes and micelles. Lasers Surg Med 2009; 41: 316-322.

[195] Broekgaarden M, Kos M, Jurg FA, van Beek AA, van Gulik TM, Heger M. Inhibition of nf-kappab in tumor cells exacerbates immune cell activation following photodynamic therapy. Int J Mol Sci 2015; 16: 19960-19977.

[196] Broekgaarden M, de Kroon AI, Gulik TM, Heger M. Development and in vitro proof-of-concept of interstitially targeted zinc- phthalocyanine liposomes for photodynamic therapy. Curr Med Chem 2014; 21: 377-391.

[197] Yang K, Gitter B, Ruger R, Wieland GD, Chen M, Liu X, Albrecht V, Fahr A. Antimicrobial peptide-modified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy. Photochem Photobiol Sci 2011; 10: 1593-1601.

[198] Ke MR, Eastel JM, Ngai KL, Cheung YY, Chan PK, Hui M, Ng DK, Lo PC. Oligolysine-conjugated zinc(ii) phthalocyanines as efficient photosensitizers for antimicrobial photodynamic therapy. Chem Asian J 2014; 9: 1868-1875.

[199] Liu F, Soh Yan Ni A, Lim Y, Mohanram H, Bhattacharjya S, Xing B. Lipopolysaccharide neutralizing peptide-porphyrin conjugates for effective photoinactivation and intracellular imaging of gram-negative bacteria strains. Bioconjug Chem 2012; 23: 1639-1647.

[200] Sun J, Deng Z, Yan A. Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun 2014; 453: 254-267.

[201] Renau TE, Leger R, Filonova L, Flamme EM, Wang M, Yen R, Madsen D, Griffith D, Chamberland S, Dudley MN, Lee VJ, Lomovskaya O, Watkins WJ, Ohta T, Nakayama K, Ishida Y. Conformationally-restricted analogues of efflux pump inhibitors that potentiate the activity of levofloxacin in pseudomonas aeruginosa. Bioorg Med Chem Lett 2003; 13: 2755-2758.

[202] Yarmush ML, Golberg A, Sersa G, Kotnik T, Miklavcic D. Electroporation-based technologies for medicine: Principles, applications, and challenges. Annu Rev Biomed Eng 2014; 16: 295-320.

[203] Heger M, van der Wal AC, Storm G, van Gemert MJ. Potential therapeutic benefits stemming from the thermal nature of irreversible electroporation of solid cancers. Hepatobiliary Pancreat Dis Int 2015; 14: 331-333.

[204] de Melo Wde C, Lee AN, Perussi JR, Hamblin MR. Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin. Photodiagnosis Photodyn Ther 2013; 10: 647-650.

[205] Kotulska M, Kulbacka J, Saczko J. Advances in photodynamic therapy assisted by electroporation. Curr Drug Metab 2013; 14: 309-318.

[206] Takasaki AA, Aoki A, Mizutani K, Schwarz F, Sculean A, Wang CY, Koshy G, Romanos G, Ishikawa I, Izumi Y. Application of antimicrobial photodynamic therapy in periodontal and peri-implant diseases. Periodontol 2000 2009; 51: 109- 140.

[207] Yin M, Li Z, Ju E, Wang Z, Dong K, Ren J, Qu X. Multifunctional upconverting nanoparticles for near-infrared triggered and synergistic antibacterial resistance therapy. Chem Commun (Camb) 2014; 50: 10488-10490.

[208] Gnach A, Lipinski T, Bednarkiewicz A, Rybka J, Capobianco JA. Upconverting nanoparticles: Assessing the toxicity. Chem Soc Rev 2015; 44: 1561-1584.

[209] Vecchio D, Gupta A, Huang L, Landi G, Avci P, Rodas A, Hamblin MR. Bacterial photodynamic inactivation mediated by methylene blue and red light is enhanced by synergistic effect of potassium iodide. Antimicrob Agents Chemother 2015; 59: 5203-5212.

[210] Demidova TN, Gad F, Zahra T, Francis KP, Hamblin MR. Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria. J Photochem Photobiol B 2005; 81: 15-25.

[211] Vecchio D, Dai T, Huang L, Fantetti L, Roncucci G, Hamblin MR. Antimicrobial photodynamic therapy with rlp068 kills methicillin-resistant staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion pdt with rlp068/cl in infected mouse skin abrasion. J Biophotonics 2013; 6: 733-742.

[212] Dai T, Tegos GP, Zhiyentayev T, Mylonakis E, Hamblin MR. Photodynamic therapy for methicillin-resistant staphylococcus aureus infection in a mouse skin abrasion model. Lasers Surg Med 2010; 42: 38-44.

[213] Orenstein A, Klein D, Kopolovic J, Winkler E, Malik Z, Keller N, Nitzan Y. The use of porphyrins for eradication of staphylococcus aureus in burn wound infections. FEMS Immunol Med Microbiol 1997; 19: 307-314.

[214] Garcia VG, Fernandes LA, Macarini VC, de Almeida JM, Martins TM, Bosco AF, Nagata MJ, Cirelli JA, Theodoro LH. Treatment of experimental periodontal disease with antimicrobial photodynamic therapy in nicotine-modified rats. J Clin Periodontol 2011; 38: 1106-1114.

[215] Hashimoto MC, Prates RA, Kato IT, Nunez SC, Courrol LC, Ribeiro MS. Antimicrobial photodynamic therapy on drug-resistant pseudomonas aeruginosa-induced infection. An in vivo study. Photochem Photobiol 2012; 88: 590-595.

[216] Chien CY, Lin CH, Chen JW, Hsu RB. Blood stream infection in patients undergoing systematic off-pump coronary artery bypass: Incidence, risk factors, outcome, and associated pathogens. Surg Infect (Larchmt) 2014; 15: 613-618.

[217] Duane TM, Kikhia RM, Wolfe LG, Ober J, Tessier JM. Understanding gram-negative central line-associated blood stream infection in a surgical trauma ICU. Am Surg 2015; 81: 816-819.

[218] Munder A, Wolbeling F, Klockgether J, Wiehlmann L, Tummler B. In vivo imaging of bioluminescent pseudomonas aeruginosa in an acute murine airway infection model. Pathog Dis 2014; 72: 74-77.

[219] St Denis TG, Dai T, Izikson L, Astrakas C, Anderson RR, Hamblin MR, Tegos GP. All you need is light: Antimicrobial photoinactivation as an evolving and emerging discovery strategy against infectious disease. Virulence 2011; 2: 509-520.

[220] Zuellig RA, Hornemann T, Othman A, Hehl AB, Bode H, Guntert T, Ogunshola OO, Saponara E, Grabliauskaite K, Jang JH, Ungethuem U, Wei Y, von Eckardstein A, Graf R, Sonda S. Deoxysphingolipids, novel biomarkers for type 2 diabetes, are cytotoxic for insulin-producing cells. Diabetes 2014; 63: 1326- 1339.

[221] Serrano C, Torres N, Valdivieso C, Castano C, Barrera M, Cabrales A. Antibiotic resistance of periodontal pathogens obtained from frequent antibiotic users. Acta Odontol Latinoam 2009; 22: 99-104.

[222] Daneman N, Gruneir A, Newman A, Fischer HD, Bronskill SE, Rochon PA, Anderson GM, Bell CM. Antibiotic use in longterm care facilities. J Antimicrob Chemother 2011; 66: 2856- 2863.

[223] Cole MR, Hobden JA, Warner IM. Recycling antibiotics into gumbos: A new combination strategy to combat multi-drugresistant bacteria. Molecules 2015; 20: 6466-6487.

[224] Tripathi P, Somashekar BS, Ponnusamy M, Gursky A, Dailey S, Kunju P, Lee CT, Chinnaiyan AM, Rajendiran TM, Ramamoorthy A. Hr-mas nmr tissue metabolomic signatures crossvalidated by mass spectrometry distinguish bladder cancer from benign disease. J Proteome Res 2013; 12: 3519-3528.

[225] Petelin M, Perkic K, Seme K, Gaspirc B. Effect of repeated adjunctive antimicrobial photodynamic therapy on subgingival periodontal pathogens in the treatment of chronic periodontitis. Lasers Med Sci 2015; 30: 1647-1656.

[226] Queiroz AC, Suaid FA, de Andrade PF, Novaes AB, Jr., Taba M, Jr., Palioto DB, Grisi MF, Souza SL. Antimicrobial photodynamic therapy associated to nonsurgical periodontal treatment in smokers: Microbiological results. J Photochem Photobiol B 2014; 141: 170-175.

[227] Sun Y, Xing D, Shen L, Sun M, Fang M, Bi L, Sui Y, Zhang Z, Cao W. Bactericidal effects of hematoporphyrin monomethyl ether-mediated photosensitization against pathogenic communities from supragingival plaque. Appl Microbiol Biotechnol 2013; 97: 5079-5087.

[228] Thierbach R, Eger T. Clinical outcome of a nonsurgical and surgical treatment protocol in different types of peri-implantitis: A case series. Quintessence Int 2013; 44: 137-148.

[229] Singh S, Nagpal R, Manuja N, Tyagi SP. Photodynamic therapy: An adjunct to conventional root canal disinfection strategies. Aust Endod J 2015; 41: 54-71.

[230] Maisch T. Resistance in antimicrobial photodynamic inactivation of bacteria. Photochem Photobiol Sci 2015; 14: 1518- 1526.

[231] Brown S. Clinical antimicrobial photodynamic therapy: Phase ii studies in chronic wounds. J Natl Compr Canc Netw 2012; 10 Suppl 2: S80-83.

[232] Lei X, Liu B, Huang Z, Wu J. A clinical study of photodynamic therapy for chronic skin ulcers in lower limbs infected with pseudomonas aeruginosa. Arch Dermatol Res 2015; 307: 49- 55.

[233] Sahu K, Sharma M, Bansal H, Dube A, Gupta PK. Topical photodynamic treatment with poly-l-lysine-chlorin p6 conjugate improves wound healing by reducing hyperinflammatory response in pseudomonas aeruginosa-infected wounds of mice. Lasers Med Sci 2013; 28: 465-471.

[234] Tardivo JP, Adami F, Correa JA, Pinhal MA, Baptista MS. A clinical trial testing the efficacy of PDT in preventing amputation in diabetic patients. Photodiagnosis Photodyn Ther 2014; 11: 342-350.

[235] Huang YY, Tanaka M, Vecchio D, Garcia-Diaz M, Chang J, Morimoto Y, Hamblin MR. Photodynamic therapy induces an immune response against a bacterial pathogen. Expert Rev Clin Immunol 2012; 8: 479-494.

[236] Redmond RW, Gamlin JN. A compilation of singlet oxygen yields from biologically relevant molecules. Photochem Photobiol 1999; 70: 391-475.

[237] Wainwright M, Phoenix DA, Marland J, Wareing DR, Bolton FJ. A study of photobactericidal activity in the phenothiazinium series. FEMS Immunol Med Microbiol 1997; 19: 75-80.

[238] Cahan R, Swissa N, Gellerman G, Nitzan Y. Photosensitizer-antibiotic conjugates. A novel class of antibacterial molecules. Photochem Photobiol 2010; 86: 418-425.

[239] Turbay MB, Rey V, Arganaraz NM, Moran Vieyra FE, Aspee A, Lissi EA, Borsarelli CD. Effect of dye localization and self-interactions on the photosensitized generation of singlet oxygen by rose bengal bound to bovine serum albumin. J Photochem Photobiol B 2014; 141: 275-282.

[240] Verma S, Sallum UW, Athar H, Rosenblum L, Foley JW, Hasan T. Antimicrobial photodynamic efficacy of side‐chain functionalized benzo [a] phenothiazinium dyes. Photochemistry and photobiology 2009; 85: 111-118.

[241] Fu XJ, Zhu YQ, Peng YB, Chen YS, Hu YP, Lu HX, Yu WR, Fang Y, Du JZ, Yao M. Enzyme activated photodynamic therapy for methicillin-resistant staphylococcus aureus infection both inv itro and in vivo. J Photochem Photobiol B 2014; 136: 72-80.

[242] Phoenix DA, Harris F. Phenothiazinium-based photosensitizers: Antibacterials of the future? Trends Mol Med 2003; 9: 283- 285.

[243] Ragàs X, Dai T, Tegos GP, Agut M, Nonell S, Hamblin MR. Photodynamic inactivation of acinetobacter baumannii using phenothiazinium dyes: In vitro and in vivo studies. Lasers in surgery and medicine 2010; 42: 384.

[244] Nitzan Y, Dror R, Ladan H, Malik Z, Kimel S, Gottfried V. Structure-activity relationship of porphines for photoinactivation of bacteria. Photochem Photobiol 1995; 62: 342-347.

[245] Fabris C, Soncin M, Mazzon E, Calzavara-Pinton P, Lia F, Giacomo C, Dei D, Tampucci S, Roncucci G, Jori G. A novel tetracationic phthalocyanine as a potential skin phototherapeutic agent. Exp Dermatol 2005; 14: 675-683.

[246] Wang M, Huang L, Sharma SK, Jeon S, Thota S, Sperandio FF, Nayka S, Chang J, Hamblin MR, Chiang LY. Synthesis and photodynamic effect of new highly photostable decacationically armed [60]- and [70]fullerene decaiodide monoadducts to target pathogenic bacteria and cancer cells. J Med Chem 2012; 55: 4274-4285.

[247] Maisch T, Eichner A, Spath A, Gollmer A, Konig B, Regensburger J, Baumler W. Fast and effective photodynamic inactivation of multiresistant bacteria by cationic riboflavin derivatives. PLoS One 2014; 9: e111792.

[248] Karygianni L, Ruf S, Follo M, Hellwig E, Bucher M, Anderson AC, Vach K, Al-Ahmad A. Novel broad-spectrum antimicrobial photoinactivation of in situ oral biofilms by visible light plus water-filtered infrared a. Appl Environ Microbiol 2014; 80: 7324-7336.

[249] Mesquita MQ, Menezes JC, Neves MG, Tome AC, Cavaleiro JA, Cunha A, Almeida A, Hackbarth S, Roder B, Faustino MA. Photodynamic inactivation of bioluminescent escherichia coli by neutral and cationic pyrrolidine-fused chlorins and isobacteriochlorins. Bioorg Med Chem Lett 2014; 24: 808-812.

[250] Arenas Y, Monro S, Shi G, Mandel A, McFarland S, Lilge L. Photodynamic inactivation of staphylococcus aureus and methicillin-resistant staphylococcus aureus with ru(ii)-based type i/type ii photosensitizers. Photodiagnosis Photodyn Ther 2013; 10: 615-625.

[251] Papastamou V, Nietzsch T, Staudte H, Orellana G, Sigusch BW. Photoinactivation of f. Nucleatum and p. Gingivalis using the ruthenium-based rd3 sensitizer and a conventional halogen lamp. Arch Oral Biol 2011; 56: 264-268.

[252] George S, Kishen A. Influence of photosensitizer solvent on the mechanisms of photoactivated killing of enterococcus faecalis. Photochem Photobiol 2008; 84: 734-740.

[253] Schafer M, Schmitz C, Facius R, Horneck G, Milow B, Funken KH, Ortner J. Systematic study of parameters influencing the action of rose bengal with visible light on bacterial cells: Comparison between the biological effect and singlet-oxygen production. Photochem Photobiol 2000; 71: 514-523.

[254] Usacheva MN, Teichert MC, Usachev YM, Sievert CE, Biel MA. Interaction of the photobactericides methylene blue and toluidine blue with a fluorophore in pseudomonas aeruginosa cells. Lasers Surg Med 2008; 40: 55-61.

[255] Jin H, Huang X, Chen Y, Zhao H, Ye H, Huang F, Xing X, Cai J. Photoinactivation effects of hematoporphyrin monomethyl ether on gram-positive and -negative bacteria detected by atomic force microscopy. Appl Microbiol Biotechnol 2010; 88: 761-770.

[256] Grinholc M, Nakonieczna J, Fila G, Taraszkiewicz A, Kawiak A, Szewczyk G, Sarna T, Lilge L, Bielawski KP. Antimicrobial photodynamic therapy with fulleropyrrolidine: Photoinactivation mechanism of staphylococcus aureus, in vitro and in vivo studies. Appl Microbiol Biotechnol 2015; 99: 4031-4043.

Share
Back to top
Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing