Photoinactivation of catalase sensitizes a wide range of bacteria to ROS-producing agents and immune cells

Dong, Pu‐Ting; Jusuf, Sebastian; Hui, Jie; Zhan, Yuewei; Zhu, Yifan; Liu, George Y.; Cheng, Ji‐Xin

doi:10.1172/jci.insight.153079

Cited by 19 publications

(22 citation statements)

References 79 publications

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“…In comparison to MRSA-infected wounds, wounds infected with MDR-PA only showed ≈1.3-logs reduction in biofilm CFU counts when treated with polarized e-bandages; combination treatment with amikacin and e-bandages did not improve bacterial killing. P. aeruginosa can mount a strong SOS response in the presence of sub-lethal H 2 O 2 concentrations, [55,56] and it has several catalase producing genes (e.g., katA, katB) which can confer protection against H 2 O 2 . These factors might explain the lower CFU reductions observed with e-bandage treatment of MDR-PA compared to MRSA infection.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Activity of Hydrogen‐Peroxide Generating Electrochemical Bandage Against Murine Wound Infections

Raval

Fleming

Mohamed

et al. 2023

Advanced Therapeutics

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Biofilms formed by antibiotic-resistant bacteria in wound beds challenge the treatment of wound infections. In this work, the activity of a novel electrochemical bandage (e-bandage) composed of carbon fabric and controlled by a wearable potentiostat, designed to continuously deliver low amounts of hydrogen peroxide (H 2 O 2 ), is evaluated against methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (MDR-PA) and mixed-species (MRSA and MDR-PA) wound infections. Wounds created on Swiss Webster mice are infected with the above-named bacteria and biofilms allow to establish in wound beds for 3 days. e-Bandages, which electrochemically reduce dissolved oxygen to H 2 O 2 when polarized at −0.6 V Ag/AgCl , are placed atop infected wound beds and polarized continuously for 48 h. Polarized e-bandage treatment results in significant reductions (p <0.001) of both monospecies and mixed-species wound infections. After e-bandage treatment, electron microscopy shows degradation of bacterial cells, and histopathology shows no obvious alterations to the inflammatory host response. Blood biochemistries show no abnormalities. Taken all together, results of this work suggest that the described H 2 O 2 -producing e-bandage can reduce in vivo MRSA, MDR-PA, and mixed-species wound biofilms, and should be further developed as a potential antibiotic-free strategy for treatment of wound infections.

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Section: Discussionmentioning

confidence: 99%

In Vivo Activity of Hydrogen‐Peroxide Generating Electrochemical Bandage Against Murine Wound Infections

Raval

Fleming

Mohamed

et al. 2023

Advanced Therapeutics

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“…Our studies have demonstrated that aBL can effectively kill a range of microorganisms without the generation of resistance to aBL becoming a significant concern (Leanse et al, 2018 ; Marasini et al, 2021 ). In addition, numerous studies have shown aBL to be compatible with conventional and non-conventional agents, illustrating its potential as an adjunct therapeutic (Leanse et al, 2020a , 2021b ; Li and Wu, 2021 ; Dong et al, 2022a , b ). The mechanism of aBL killing of microorganisms is currently understood to be mediated via photoexcitation of endogenous chromophores (primarily porphyrins) to induce the production of reactive oxygen species (ROS) that damage the internal structures of the microbial cell (Wang et al, 2017b ; Chu et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism of aBL killing of microorganisms is currently understood to be mediated via photoexcitation of endogenous chromophores (primarily porphyrins) to induce the production of reactive oxygen species (ROS) that damage the internal structures of the microbial cell (Wang et al, 2017b ; Chu et al, 2019 ). More recently, other molecular targets of aBL have been identified, such as staphyloxanthin in Staphylococcus aureus and catalase in numerous microbes, both of which have been shown to sensitize microbes to ROS (Dong et al, 2019 , 2022a , b ; Hui et al, 2020 ). aBL elicits its microbicidal effects much more rapidly than traditional antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Blue Light for Prevention and Treatment of Highly Invasive Vibrio vulnificus Burn Infection in Mice

et al. 2022

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Vibrio vulnificus is an invasive marine bacterium that causes a variety of serious infectious diseases. With the increasing multidrug-resistant variants, treatment of V. vulnificus infections is becoming more difficult. In this study, we explored antimicrobial blue light (aBL; 405 nm wavelength) for the treatment of V. vulnificus infections. We first assessed the efficacy of aBL against five strains of V. vulnificus in vitro. Next, we identified and quantified intracellular porphyrins in V. vulnificus to provide mechanistic insights. Additionally, we measured intracellular reactive oxygen species (ROS) production and bacterial membrane permeabilization following aBL exposures. Lastly, we conducted a preclinical study to investigate the efficacy and safety of aBL for the prevention and treatment of burn infections caused by V. vulnificus in mice. We found that aBL effectively killed V. vulnificus in vitro in both planktonic and biofilm states, with up to a 5.17- and 4.57-log10 CFU reduction being achieved, respectively, following an aBL exposure of 216 J/cm2. Protoporphyrin IX and coproporphyrins were predominant in all the strains. Additionally, intracellular ROS was significantly increased following aBL exposures (P < 0.01), and there was evidence of aBL-induced permeabilization of the bacterial membrane (P < 0.0001). In the preclinical studies, we found that female mice treated with aBL 30 min after bacterial inoculation showed a survival rate of 81% following 7 days of observation, while only 28% survival was observed in untreated female mice (P < 0.001). At 6 h post-inoculation, an 86% survival was achieved in aBL-treated female mice (P = 0.0002). For male mice, 86 and 63% survival rates were achieved when aBL treatment was given 30 min and 6 h after bacterial inoculation, respectively, compared to 32% survival in the untreated mice (P = 0.0004 and P = 0.04). aBL did not reduce cellular proliferation or induce apoptosis. We found five cytokines were significantly upregulated in the males after aBL treatment, including MCSF (P < 0.001), MCP-5 (P < 0.01), TNF RII (P < 0.01), CXCL1 (P < 0.01), and TIMP-1 (P < 0.05), and one in the females (TIMP-1; P < 0.05), suggesting that aBL may induce certain inflammatory processes. In conclusion, aBL may potentially be applied to prevent and treat V. vulnificus infections.

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“…Intensities between 50-100 mW/cm 2 have shown potent bactericidal efficacy in vitro in a dose-dependent manner 29,33,34,36,38,39 . However, when advanced to in vivo testing on animal models, even 200 mW/cm 2 — considered the Maximum Permissible Exposure (MPE) level given by the American National Standard Institute (ANSI) guidelines 42 — at 300 J/cm 2 levels results in only moderate (< 2-log 10 ) reductions 32,41 . These high-intensity levels pose a serious risk of photothermal damage, more prominent under repeated dosing to prevent bacterial relapse 32,41,43 .…”

mentioning

confidence: 99%

“…However, when advanced to in vivo testing on animal models, even 200 mW/cm 2 — considered the Maximum Permissible Exposure (MPE) level given by the American National Standard Institute (ANSI) guidelines 42 — at 300 J/cm 2 levels results in only moderate (< 2-log 10 ) reductions 32,41 . These high-intensity levels pose a serious risk of photothermal damage, more prominent under repeated dosing to prevent bacterial relapse 32,41,43 . Moreover, the demand for high irradiance places substantial practical constraints on light sources, especially for large wounds which requires high total power and proper thermal management for large-area illumination.…”

mentioning

confidence: 99%

Antimicrobial blue light-bathing therapy for wound infection control

Hui,

Moon,

Dong

et al. 2024

Preprint

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The prevalence of antibiotic resistance and tolerance in wound infection management poses a serious and growing health threat, necessitating the exploration of alternative approaches. Antimicrobial blue light therapy offers an appealing, non-pharmacological solution. However, its practical application has been hindered by the requirement for high irradiance levels, which particularly raises safety concerns. Here, we introduce a light-bathing strategy that employs prolonged, continuous exposure to blue light at an irradiance range lower by more than an order of magnitude (5 mW/cm2). This method consistently applies bacteriostatic pressure, keeping wound bioburden low, all while minimizing photothermal risks. Leveraging tailor-made, wearable light-emitting patches, we conducted preclinical trials on rat models of wound infection, demonstrating its safety and efficacy for suppressing infections induced by methicillin-resistantS. aureusand multidrug-resistantP. aeruginosa. Our results pave a new way for the application of blue light therapy in wound care.

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Photoinactivation of catalase sensitizes a wide range of bacteria to ROS-producing agents and immune cells

Cited by 19 publications

References 79 publications

In Vivo Activity of Hydrogen‐Peroxide Generating Electrochemical Bandage Against Murine Wound Infections

In Vivo Activity of Hydrogen‐Peroxide Generating Electrochemical Bandage Against Murine Wound Infections

Antimicrobial Blue Light for Prevention and Treatment of Highly Invasive Vibrio vulnificus Burn Infection in Mice

Antimicrobial blue light-bathing therapy for wound infection control

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