Aloe-Emodin-Mediated Photodynamic Therapy Attenuates Sepsis-Associated Toxins in Selected Gram-Positive Bacteria In Vitro
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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 grampositive 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 bacteriainfected 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 μg/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 proinflammatory cytokines, hemolytic activities, and inhibiting the expressions of toxins that cause sepsis.
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 grampositive 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 bacteriainfected 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 μg/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 proinflammatory cytokines, hemolytic activities, and inhibiting the expressions of toxins that cause sepsis.
참고문헌 (36)
- Berg D, "Recent advances in understanding and managing sepsis", F1000Res, 7 (2018)
- Brady J, "Role of the adaptive immune response in sepsis", Intensive Care Med. Exp, 8, pp.20~ (2020)
- Cabrera-Perez J, "Impact of sepsis on CD4 T cell immunity", J. Leukoc. Biol, 96, pp.767~777 (2014)
- Al Achkar M, "Pantoea species sepsis associated with sickle cell crisis in a pregnant woman with a history of pica", Am. J. Case Rep, 13, pp.26~28 (2012)
- de Oliveira TH, "Sepsis induced by Staphylococcus aureus : participation of biomarkers in a murine model", Med. Sci. Monit, 21, pp.345~355 (2015)
- Minasyan H, "Sepsis : mechanisms of bacterial injury to the patient", Scand. J. Trauma Resusc. Emerg. Med, 27, pp.19~ (2019)
- Martin GS, "Sepsis, severe sepsis and septic shock : changes in incidence, pathogens and outcomes", Expert. Rev. Anti Infect. Ther, 10, pp.701~706 (2012)
- Lv Z, "Achieving efficient photodynamic therapy under both normoxia and hypoxia using cyclometalated Ru(ii)photosensitizer through type I photochemical process", Chem. Sci, 9, pp.502~512 (2018)
- Dong X, "Emodin : A review of its pharmacology, toxicity and pharmacokinetics", Phytother. Res, 30, pp.1207~1218 (2016)
- Ma W, "The effects of aloe emodin-mediated antimicrobial photodynamic therapy on drugsensitive and resistant Candida albicans", Photochem. Photobiol. Sci, 19, pp.485~494 (2020)
- Chen Q, "Photodynamic therapy mediated by Aloe-Emodin inhibited angiogenesis and cell metastasis through activating MAPK signaling pathway on HUVECs", Technol. Cancer Res. Treat, 17, pp.1533033818785512~ (2018)
- Zang L, "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, pp.1088~1094 (2017)
- Jiang L, "Aloe-emodin attenuates Staphylococcus aureus pathogenicity by interfering with the oligomerization of α-toxin", Front. Cell. Infect. Microbiol, 9, pp.157~ (2019)
- Zou J, "Enterococcus faecalis infection activates phosphatidylinositol 3-kinase signaling to block apoptotic cell death in macrophages", Infect. Immun, 82, pp.5132~5142 (2014)
- Cabral GRdA, "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, pp.1936~ (2018)
- Rasko DA, "Anti-virulence strategies to combat bacteria-mediated disease", Nat. Rev. Drug Discov, 9, pp.117~128 (2010)
- Ventola CL, "The antibiotic resistance crisis : part 1 : causes and threats", P T, 40, pp.277~283 (2015)
- Qiu J, "Capsaicin protects mice from community-associated methicillin-resistant Staphylococcus aureus pneumonia", PLoS One, 7, pp.e33032~ (2012)
- Kong C, "Targeting Staphylococcus aureus toxins : A potential form of anti-virulence therapy", Toxins(Basel), 8, pp.72~ (2016)
- Romp E, "Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis", Cell. Mol. Life Sci, 77, pp.3841~3858 (2020)
- Sharma B, "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, pp.8515~8524 (2020)
- Hall CW, "Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria", FEMS Microbiol. Rev, 41, pp.276~301 (2017)
- Delle-Bovi RJ, "Rapid method for the determination of total monosaccharide in Enterobacter cloacae strains using fourier transform infrared spectroscopy", Am. J. Anal. Chem, 2, pp.212~216 (2011)
- Khatoon Z, "Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention", Heliyon, 4, pp.e01067~ (2018)
- Sobisch L-Y, "Biofilm forming antibiotic resistant grampositive pathogens isolated from surfaces on the international space station", Front. Microbiol, 10, pp.543~ (2019)
- Catão MHCdV, "In vitro evaluation of the antibacterial effect of photodynamic therapy with methylene blue", Pesqui. Bras. Odontopediatria Clin. Integr, 20 (2020)[DOI]
- Otieno W, "Hypocrellin B-mediated photodynamic inactivation of Gram-positive antibioticresistant bacteria : an in vitro study", Photobiomodul. Photomed. Laser Surg, 38, pp.36~42 (2020)
- Lambden S, "Bench to bedside review : therapeutic modulation of nitric oxide in sepsis—an update", Intensive Care Med. Exp, 7, pp.64~ (2019)
- Hullmann G, "Role of IL-1B in TLR4-mediated MCP-1expression : renal sepsis", Am. J. Biomed, 3, pp.22~31 (2015)
- Franco DM, "Plasma interleukin‐6 concentration for the diagnosis of sepsis in critically ill adults", Cocharne Database Syst. Rev, 4, pp.CD011811~ (2019)
- Hotchkiss RS, "Sepsis and septic shock", Nat. Rev. Dis. Primers, 2, pp.16045~ (2016)
- Huang XQ, "Sepsis secondary to multifocal Enterococcusfaecium infection : a case report", Medicine, 99, pp.e19811~ (2020)
- van der Poll T, "Pathogenesis, treatment, and prevention of pneumococcal pneumonia", Lancet, 374, pp.1543~1556 (2009)
- Van Tyne D, "Structure, function, and biology of the Enterococcus faecalis cytolysin", Toxins(Basel), 5, pp.895~911 (2013)
- Divyakolu S, "Hemolysins of Staphylococcus aureus—An update on their biology, role in pathogenesis and as targets for anti-virulence therapy", Adv. Infect. Dis, 9, pp.80~104 (2019)
- Nishimoto AT, "Pneumolysin : pathogenesis and therapeutic target", Front. Microbiol, 11, pp.1543~ (2020)