Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
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Antimicrobial Photodynamic Therapy on Pseudomonas aeruginosa Using a Diode Laser and PhotoMed, Methyl Pheophorbide A, or Radachlorin®

다이오드 레이저와 PhotoMed, Methyl Pheophorbide A, Radachlorin®을 이용한 녹농균에 대한 항균 광역학 요법

  • Young-Kyu SONG (PDT Research Center, Dr.inB Co.) ;
  • Keun-Dol YOOK (Department of Clinical Laboratory Science, Daejeon Health University) ;
  • Ji-Won KIM (Department of Radiological Science, Daejeon Health University)
  • 송영규 (닥터아이앤비 광역학치료연구센터) ;
  • 육근돌 (대전보건대학교 임상병리과) ;
  • 김지원 (대전보건대학교 방사선과)
  • Received : 2024.01.28
  • Accepted : 2024.02.07
  • Published : 2024.03.31
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Abstract

Photodynamic therapy (PDT) activates intracellular oxygen using a photosensitizer activated by light of a specific wavelength and is a potential means of treating wound infections caused by antibiotic-resistant bacteria. Pseudomonas aeruginosa (P. aeruginosa) is typically non-pathogenic in healthy individuals but can induce severe illnesses like sepsis in the immunocompromised. Antibiotics have been conventionally used to treat P. aeruginosa infections, but increasing antibiotic resistance caused by drug misuse poses a growing challenge to the management of these infections. This study aimed to investigate the ability of PDT using photosensitizers (PhotoMed, Methyl pheophorbide A, or Radachlorin®) and a diode laser to inhibit P. aeruginosa. Suspensions of P. aeruginosa and a photosensitizer were inoculated into Petri dishes and incubated for 30 minutes. Samples were then irradiated with the laser at 3 J/cm2, and after incubation, colony areas were measured. P. aeruginosa killing rates were 79.65% for PhotoMed, 47.36% for Methyl pheophorbide A, and 40.91% for Radachlorin®. This study shows that PDT using a diode laser and a photosensitizer constitutes an effective practical therapeutic approach for inhibiting P. aeruginosa.

광역학 요법(photodynamic therapy)은 특정 파장의 빛에 의해 활성화되는 광민감제(photosensitizer)를 사용하여 세포 내 산소를 활성화시키는 치료 방법으로, 항생제 내성균에 의한 상처 감염의 치료에 유망한 접근 방법이다. 일반적으로 건강한 사람에게 비병원성인 녹농균(Pseudomonas aeruginosa, P. aeruginosa)은 특정 병원성 징후를 보이지 않지만, 피부 손상이나 면역력이 저하된 사람들에서는 패혈증과 같은 심각한 질병을 유발할 수 있다. 항생제는 P. aeruginosa 감염에 대한 전통적인 치료법이나 약물 오용으로 인한 항생제 내성의 증가는 이러한 감염을 관리하는 데 큰 어려움을 준다. 본 연구에서는 P. aeruginosa의 억제제로서 광민감제(PhotoMed, Methyl pheophorbide A, Radachlorin®)와 다이오드 레이저를 이용한 광역학 치료 효과를 조사하는 것을 목표로 했다. P. aeruginosa 현탁액과 광민감제(PhotoMed, Methyl pheophorbide A, Radachlorin®)를 페트리 접시에 접종하여 30분 후 다이오드 레이저를 사용하여 3 J/cm2의 에너지 밀도로 조사했다. 그 결과, P. aeruginosa는 PhotoMed에서 79.65%, Methyl pheophorbide A에서 47.36%, Radachlorin®에서 40.91%의 사멸률을 보였다. 이번 연구는 P. aeruginosa를 억제하기 위한 가장 효과적인 접근법이 PhotoMed와 다이오드 레이저를 이용한 광역학 치료임을 보여준다.

Keywords

Acknowledgement

This paper was supported by the Meister support project of Daejeon Health University in 2023.

References

  1. Wu M, Li X. Klebsiella pneumoniae and Pseudomonas aeruginosa. In: Tang YW, Sussman M, Liu D, Poxton I, Schwartzman J, editors. Molecular medical microbiology. 2nd ed. Elsevier: 2015. p.1547-1564.
  2. Diggle SP, Whiteley M. Microbe profile: Pseudomonas aeruginosa: opportunistic pathogen and lab rat. Microbiology (Reading). 2020;166:30-33. https://doi.org/10.1099/mic.0.000860 Erratum in: Microbiology (Reading). 2021;167:001073. https://doi.org/10.1099/mic.0.001073
  3. Rossolini GM, Mantengoli E. Treatment and control of severe infections caused by multiresistant Pseudomonas aeruginosa. Clin Microbiol Infect. 2005;11 Suppl 4:17-32. https://doi.org/10.1111/j.1469-0691.2005.01161.x
  4. Sheng Z. Prevention of multiple organ dysfunction syndrome in patients with extensive deep burns. Chin J Traumatol. 2002;5:195-199.
  5. Chevalier S, Bouffartigues E, Bodilis J, Maillot O, Lesouhaitier O, Feuilloley MGJ, et al. Structure, function and regulation of Pseudomonas aeruginosa porins. FEMS Microbiol Rev. 2017;41:698-722. https://doi.org/10.1093/femsre/fux020
  6. Kunz Coyne AJ, El Ghali A, Holger D, Rebold N, Rybak MJ. Therapeutic strategies for emerging multidrug-resistant Pseudomonas aeruginosa. Infect Dis Ther. 2022;11:661-682. https://doi.org/10.1007/s40121-022-00591-2
  7. Mulcahy LR, Burns JL, Lory S, Lewis K. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J Bacteriol. 2010;192:6191-6199. https://doi.org/10.1128/JB.01651-09
  8. Yanten N, Vilches S, Palavecino CE. Photodynamic therapy for the treatment of Pseudomonas aeruginosa infections: a scoping review. Photodiagnosis Photodyn Ther. 2023;44:103803. https://doi.org/10.1016/j.pdpdt.2023.103803
  9. Topaloglu N, Gulsoy M, Yuksel S. Antimicrobial photodynamic therapy of resistant bacterial strains by indocyanine green and 809-nm diode laser. Photomed Laser Surg. 2013;31:155-162. https://doi.org/10.1089/pho.2012.3430
  10. Dai T, Huang YY, Hamblin MR. Photodynamic therapy for localized infections--state of the art. Photodiagnosis Photodyn Ther. 2009;6:170-188. https://doi.org/10.1016/j.pdpdt.2009.10.008
  11. Akilov OE, Kosaka S, O'Riordan K, Song X, Sherwood M, Flotte TJ, et al. The role of photosensitizer molecular charge and structure on the efficacy of photodynamic therapy against Leishmania parasites. Chem Biol. 2006;13:839-847. https://doi.org/10.1016/j.chembiol.2006.06.008
  12. Fekrazad R, Zare H, Mohammadi Sepahvand S, Morsali P. The effect of antimicrobial photodynamic therapy with Radachlorin® on Staphylococcus aureus and Escherichia coli: an in vitro study. J Lasers Med Sci. 2014;5:82-85.
  13. Smijs T, Dame Z, de Haas E, Aans JB, Pavel S, Sterenborg H. Photodynamic and nail penetration enhancing effects of novel multifunctional photosensitizers designed for the treatment of onychomycosis. Photochem Photobiol. 2014;90:189-200. https://doi.org/10.1111/php.12196
  14. Lee Y, Baron ED. Photodynamic therapy: current evidence and applications in dermatology. Semin Cutan Med Surg. 2011;30:199-209. https://doi.org/10.1016/j.sder.2011.08.001
  15. Dahle J, Steen HB, Moan J. The mode of cell death induced by photodynamic treatment depends on cell density. Photochem Photobiol. 1999;70:363-367. https://doi.org/10.1111/j.1751-1097.1999.tb08150.x
  16. Lee C, Kim J, Jeong CH, Na YJ, Kim IH, Lee SY, et al. Photodynamic therapy in the management of cervical intraepithelial neoplasia. Korean J Gynecol Oncol Colposc. 2004;15:85-91. https://doi.org/10.3802/kjgoc.2004.15.2.85
  17. Fujishima I, Sakai T, Tanaka T, Ryu H, Uemura K, Fujishima Y, et al. Photodynamic therapy using pheophorbide a and Nd:YAG laser. Neurol Med Chir (Tokyo). 1991;31:257-263. https://doi.org/10.2176/nmc.31.257
  18. Allison RR, Moghissi K. Photodynamic therapy (PDT): PDT mechanisms. Clin Endosc. 2013;46:24-29. https://doi.org/10.5946/ce.2013.46.1.24
  19. Zhao Y, Lu Z, Dai X, Wei X, Yu Y, Chen X, et al. Glycomimetic-conjugated photosensitizer for specific Pseudomonas aeruginosa recognition and targeted photodynamic therapy. Bioconjug Chem. 2018;29:3222-3230. https://doi.org/10.1021/acs.bioconjchem.8b00600
  20. Yang T, Tan Y, Zhang W, Yang W, Luo J, Chen L, et al. Effects of ALA-PDT on the healing of mouse skin wounds infected with Pseudomonas aeruginosa and its related mechanisms. Front Cell Dev Biol. 2020;8:585132. https://doi.org/10.3389/fcell.2020.585132
  21. Kwon PS. Antimicrobial effects of 5-aminolevulinic acid mediated photodynamic therapy against pathogenic bacteria. Korean J Clin Lab Sci. 2022;54:273-278. https://doi.org/10.15324/kjcls.2022.54.4.273
  22. Perez-Laguna V, Garcia-Luque I, Ballesta S, Perez-Artiaga L, Lampaya-Perez V, Rezusta A, et al. Photodynamic therapy using methylene blue, combined or not with gentamicin, against Staphylococcus aureus and Pseudomonas aeruginosa. Photodiagnosis Photodyn Ther. 2020;31:101810. https://doi.org/10.1016/j.pdpdt.2020.101810
  23. Fekrazad R, Zare H, Vand SM. Photodynamic therapy effect on cell growth inhibition induced by Radachlorin and toluidine blue O on Staphylococcus aureus and Escherichia coli: an in vitro study. Photodiagnosis Photodyn Ther. 2016;15:213-217. https://doi.org/10.1016/j.pdpdt.2016.07.001
  24. Malik Z, Hanania J, Nitzan Y. Bactericidal effects of photo-activated porphyrins--an alternative approach to antimicrobial drugs. J Photochem Photobiol B. 1990;5:281-293. https://doi.org/10.1016/1011-1344(90)85044-w
  25. 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. https://doi.org/10.1111/j.1751-1097.2012.01137.x
  26. Usacheva MN, Teichert MC, Biel MA. Comparison of the methylene blue and toluidine blue photobactericidal efficacy against gram-positive and gram-negative microorganisms. Lasers Surg Med. 2001;29:165-173. https://doi.org/10.1002/lsm.1105
  27. Guest RL, Lee MJ, Wang W, Silhavy TJ. A periplasmic phospholipase that maintains outer membrane lipid asymmetry in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 2023;120:e2302546120. https://doi.org/10.1073/pnas.2302546120
  28. Thakuri PS, Joshi R, Basnet S, Pandey S, Taujale SD, Mishra N. Antibacterial photodynamic therapy on Staphylococcus aureus and Pseudomonas aeruginosa in-vitro. Nepal Med Coll J. 2011;13:281-284.