DOI QR코드

DOI QR Code

Aloe-Emodin-Mediated Photodynamic Therapy Attenuates Sepsis-Associated Toxins in Selected Gram-Positive Bacteria In Vitro

  • Otieno, Woodvine (Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center) ;
  • Liu, Chengcheng (Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center) ;
  • Ji, Yanhong (Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center)
  • Received : 2021.05.20
  • Accepted : 2021.07.22
  • Published : 2021.09.28

Abstract

Sepsis is an acute inflammatory response that leads to life-threatening complications if not quickly and adequately treated. Cytolysin, hemolysin, and pneumolysin are toxins produced by gram-positive bacteria and are responsible for resistance to antimicrobial drugs, cause virulence and lead to sepsis. This work assessed the effects of aloe-emodin (AE) and photodynamic therapy (PDT) on sepsis-associated gram-positive bacterial toxins. Standard and antibiotic-resistant Enterococcus faecalis, Staphylococcus aureus, and Streptococcus pneumonia bacterial strains were cultured in the dark with varying AE concentrations and later irradiated with 72 J/cm-2 light. Colony and biofilm formation was determined. CCK-8, Griess reagent reaction, and ELISA assays were done on bacteria-infected RAW264.7 cells to determine the cell viability, NO, and IL-1β and IL-6 pro-inflammatory cytokines responses, respectively. Hemolysis and western blot assays were done to determine the effect of treatment on hemolysis activity and sepsis-associated toxins expressions. AE-mediated PDT reduced bacterial survival in a dose-dependent manner with 32 ㎍/ml of AE almost eliminating their survival. Cell proliferation, NO, IL-1β, and IL-6 cytokines production were also significantly downregulated. Further, the hemolytic activities and expressions of cytolysin, hemolysin, and pneumolysin were significantly reduced following AE-mediated PDT. In conclusion, combined use of AE and light (435 ± 10 nm) inactivates MRSA, S. aureus (ATCC 29213), S. pneumoniae (ATCC 49619), MDR-S. pneumoniae, E. faecalis (ATCC 29212), and VRE (ATCC 51299) in an AE-dose dependent manner. AE and light are also effective in reducing biofilm formations, suppressing pro-inflammatory cytokines, hemolytic activities, and inhibiting the expressions of toxins that cause sepsis.

Keywords

References

  1. Berg D, Gerlach H. 2018. Recent advances in understanding and managing sepsis. F1000Res. 7: F1000 Faculty Rev-1570.
  2. Brady J, Horie S, Laffey JG. 2020. Role of the adaptive immune response in sepsis. Intensive Care Med. Exp. 8: 20. https://doi.org/10.1186/s40635-020-00309-z
  3. Cabrera-Perez J, Condotta SA, Badovinac VP, Griffith TS. 2014. Impact of sepsis on CD4 T cell immunity. J. Leukoc. Biol. 96: 767-777. https://doi.org/10.1189/jlb.5MR0114-067R
  4. Al Achkar M, Rogers JS, Muszynski MJ. 2012. Pantoea species sepsis associated with sickle cell crisis in a pregnant woman with a history of pica. Am. J. Case Rep. 13: 26-28. https://doi.org/10.12659/AJCR.882588
  5. de Oliveira TH, Amorin AT, Rezende IS, Santos Barbosa M, Martins HB, Brito AK, et al. 2015. Sepsis induced by Staphylococcus aureus: participation of biomarkers in a murine model. Med. Sci. Monit. 21: 345-355. https://doi.org/10.12659/MSM.892528
  6. Minasyan H. 2019. Sepsis: mechanisms of bacterial injury to the patient. Scand. J. Trauma Resusc. Emerg. Med. 27: 19. https://doi.org/10.1186/s13049-019-0596-4
  7. Martin GS. 2012. Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes. Expert. Rev. Anti Infect. Ther. 10: 701-706. https://doi.org/10.1586/eri.12.50
  8. Lv Z, Wei H, Li Q, Su X, Liu S, Zhang KY, et al. 2018. Achieving efficient photodynamic therapy under both normoxia and hypoxia using cyclometalated Ru(ii) photosensitizer through type I photochemical process. Chem. Sci. 9: 502-512. https://doi.org/10.1039/C7SC03765A
  9. Dong X, Fu J, Yin X, Cao S, Li X, Lin L, et al. 2016. Emodin: A review of its pharmacology, toxicity and pharmacokinetics. Phytother. Res. 30: 1207-1218. https://doi.org/10.1002/ptr.5631
  10. Ma W, Liu C, Li J, Hao M, Ji Y, Zeng X. 2020. The effects of aloe emodin-mediated antimicrobial photodynamic therapy on drug-sensitive and resistant Candida albicans. Photochem. Photobiol. Sci. 19: 485-494. https://doi.org/10.1039/C9PP00352E
  11. Chen Q, Li KT, Tian S, Yu TH, Yu LH, Lin HD, et al. 2018. Photodynamic therapy mediated by Aloe-Emodin inhibited angiogenesis and cell metastasis through activating MAPK signaling pathway on HUVECs. Technol. Cancer Res. Treat. 17: 1533033818785512.
  12. Zang L, Zhao H, Ji X, Cao W, Zhang Z, Meng P. 2017. Photophysical properties, singlet oxygen generation efficiency and cytotoxic effects of aloe emodin as a blue light photosensitizer for photodynamic therapy in dermatological treatment. Photochem. Photobiol. Sci. 16: 1088-1094. https://doi.org/10.1039/C6PP00453A
  13. Jiang L, Yi T, Shen Z, Teng Z, Wang J. 2019. Aloe-emodin attenuates Staphylococcus aureus pathogenicity by interfering with the oligomerization of α-toxin. Front. Cell. Infect. Microbiol. 9: 157. https://doi.org/10.3389/fcimb.2019.00157
  14. Zou J, Shankar NJI, immunity. 2014. Enterococcus faecalis infection activates phosphatidylinositol 3-kinase signaling to block apoptotic cell death in macrophages. Infect. Immun. 82: 5132-5142. https://doi.org/10.1128/IAI.02426-14
  15. Cabral GRdA, Wang ZT, Sibley LD, DaMatta RA. 2018. Inhibition of nitric oxide production in activated macrophages caused by Toxoplasma gondii infection occurs by distinct mechanisms in different mouse macrophage cell lines. Front. Microbiol. 9: 1936. https://doi.org/10.3389/fmicb.2018.01936
  16. Rasko DA, Sperandio V. 2010. Anti-virulence strategies to combat bacteria-mediated disease. Nat. Rev. Drug Discov. 9: 117-128. https://doi.org/10.1038/nrd3013
  17. Ventola CL. 2015. The antibiotic resistance crisis: part 1: causes and threats. P T 40: 277-283.
  18. Qiu J, Niu X, Wang J, Xing Y, Leng B, Dong J, et al. 2012. Capsaicin protects mice from community-associated methicillin-resistant Staphylococcus aureus pneumonia. PLoS One 7: e33032. https://doi.org/10.1371/journal.pone.0033032
  19. Kong C, Neoh HM, Nathan S. 2016. Targeting Staphylococcus aureus toxins: A potential form of anti-virulence therapy. Toxins (Basel) 8: 72. https://doi.org/10.3390/toxins8030072
  20. Romp E, Arakandy V, Fischer J, Wolz C, Siegmund A, Loffler B, et al. 2020. Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis. Cell. Mol. Life Sci. 77: 3841-3858. https://doi.org/10.1007/s00018-019-03393-x
  21. Sharma B, Thakur V, Kaur G, Chaudhary GR. 2020. Efficient photodynamic therapy against Gram-positive and Gram-negative bacteria using rose bengal encapsulated in metallocatanionic vesicles in the presence of visible light. ACS Appl. Bio Mater. 12: 8515-8524.
  22. Hall CW, Mah TF. 2017. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol. Rev. 41: 276-301. https://doi.org/10.1093/femsre/fux010
  23. Delle-Bovi RJ, Smits A, Pylypiw HM. 2011. Rapid method for the determination of total monosaccharide in Enterobacter cloacae strains using fourier transform infrared spectroscopy. Am. J. Anal. Chem. 2: 212-216. https://doi.org/10.4236/ajac.2011.22025
  24. Khatoon Z, McTiernan CD, Suuronen EJ, Mah TF, Alarcon EI. 2018. Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon 4: e01067. https://doi.org/10.1016/j.heliyon.2018.e01067
  25. Sobisch L-Y, Rogowski KM, Fuchs J, Schmieder W, Vaishampayan A, Oles P, et al. 2019. Biofilm forming antibiotic resistant gram-positive pathogens isolated from surfaces on the international space station. Front. Microbiol. 10: 543. https://doi.org/10.3389/fmicb.2019.00543
  26. Catao MHCdV, Batista ALA. 2020. In vitro evaluation of the antibacterial effect of photodynamic therapy with methylene blue. Pesqui. Bras. Odontopediatria Clin. Integr. 20. doi.org/10.1590/pboci.2020.073.
  27. Otieno W, Liu C, Deng H, Li J, Zeng X, Ji Y. 2020. Hypocrellin B-mediated photodynamic inactivation of Gram-positive antibiotic-resistant bacteria: an in vitro study. Photobiomodul. Photomed. Laser Surg. 38: 36-42. https://doi.org/10.1089/photob.2019.4656
  28. Lambden S. 2019. Bench to bedside review: therapeutic modulation of nitric oxide in sepsis-an update. Intensive Care Med. Exp. 7: 64. https://doi.org/10.1186/s40635-019-0274-x
  29. Hullmann G, Azfer M, Hensley J, Bergese A, Lefer JJAJoB. 2015. Role of IL-1B in TLR4-mediated MCP-1expression: renal sepsis. Am. J. Biomed. 3: 22-31.
  30. Franco DM, Arevalo-Rodriguez I, i Figuls MR, Oleas NGM, Nuvials X, Zamora JJCDoSR. 2019. Plasma interleukin-6 concentration for the diagnosis of sepsis in critically ill adults. Cocharne Database Syst. Rev. 4: CD011811.
  31. Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. 2016. Sepsis and septic shock. Nat. Rev. Dis. Primers 2: 16045. https://doi.org/10.1038/nrdp.2016.45
  32. Huang XQ, Qiu JK, Wang CH, Pan L, Xu JK, Pan XH, et al. 2020. Sepsis secondary to multifocal Enterococcusfaecium infection: a case report. Medicine 99: e19811. https://doi.org/10.1097/MD.0000000000019811
  33. van der Poll T, Opal SM. 2009. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet 374: 1543-1556. https://doi.org/10.1016/S0140-6736(09)61114-4
  34. Van Tyne D, Martin MJ, Gilmore MS. 2013. Structure, function, and biology of the Enterococcus faecalis cytolysin. Toxins (Basel) 5: 895-911. https://doi.org/10.3390/toxins5050895
  35. Divyakolu S, Chikkala R, Ratnakar KS, Sritharan V. 2019. Hemolysins of Staphylococcus aureus-An update on their biology, role in pathogenesis and as targets for anti-virulence therapy. Adv. Infect. Dis. 9: 80-104. https://doi.org/10.4236/aid.2019.92007
  36. Nishimoto AT, Rosch JW, Tuomanen EI. 2020. Pneumolysin: pathogenesis and therapeutic target. Front. Microbiol. 11: 1543. https://doi.org/10.3389/fmicb.2020.01543

Cited by

  1. Antimicrobial Effect of Phytochemicals from Edible Plants vol.9, pp.11, 2021, https://doi.org/10.3390/pr9112089