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Photoinactivation of catalase sensitizes a wide range of bacteria to ROS-producing agents and immune cells
Pu-Ting Dong, Sebastian Jusuf, Jie Hui, Yuewei Zhan, Yifan Zhu, George Y. Liu, Ji-Xin Cheng
Pu-Ting Dong, Sebastian Jusuf, Jie Hui, Yuewei Zhan, Yifan Zhu, George Y. Liu, Ji-Xin Cheng
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Research Article Infectious disease Microbiology

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

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Abstract

Bacteria have evolved to cope with the detrimental effects of ROS using their essential molecular components. Catalase, a heme-containing tetramer protein expressed universally in most aerobic bacteria, plays an indispensable role in scavenging excess hydrogen peroxide (H2O2). Here, through use of wild-type and catalase-deficient mutants, we identified catalase as an endogenous therapeutic target of 400–420 nm blue light. Catalase residing inside bacteria could be effectively inactivated by blue light, subsequently rendering the pathogens extremely vulnerable to H2O2 and H2O2-producing agents. As a result, photoinactivation of catalase and H2O2 synergistically eliminated a wide range of catalase-positive planktonic bacteria and P. aeruginosa inside biofilms. In addition, photoinactivation of catalase was shown to facilitate macrophage defense against intracellular pathogens. The antimicrobial efficacy of catalase photoinactivation was validated using a Pseudomonas aeruginosa–induced mouse abrasion model. Taken together, our findings offer a catalase-targeting phototherapy approach against multidrug-resistant bacterial infections.

Authors

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

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Figure 6

Photoinactivation of catalase assists macrophages to eliminate intracellular bacteria.

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Photoinactivation of catalase assists macrophages to eliminate intracell...
(A–C) Confocal images of live (SYTO 9, A), dead (PI, B), and corresponding transmission images (C) of intracellular MRSA USA300 inside RAW 264.7 macrophages after MRSA USA300 infected RAW 264.7 cells for 1 hour at a MOI of 100 in serum-free DMEM. (D–F) Confocal images of live (SYTO 9, D), dead (PI, E), and corresponding transmission images (F) of intracellular MRSA USA300 inside RAW 264.7 macrophages after 410 nm–exposed MRSA USA300 infected RAW 264.7 cells for 1 hour at an MOI of 100. 410 nm: 35 mW/cm2, 8 minutes. (G and H) Quantitative analysis of the amount of live/dead MRSA inside single RAW 264.7 cells from the above 2 scenarios. Imaging result was a representative of 2 biological repeats. (I) CFU/mL of intracellular MRSA USA300 after MRSA (with/without 410 nm exposure) infected RAW 264.7 cells for 4 hours at an MOI of 20. (J) CFU/mL of intracellular P. aeruginosa after P. aeruginosa PAO1 (with/without 410 nm exposure) infected RAW 264.7 cells for 4 hours at an MOI of 20. (K) Survival percentage of uninfected RAW 264.7 cells with/without 410 nm exposure. 410 nm: 50 mW/cm2. Data: Mean + SD from 3 replicates for panels I–K. Significant difference was determined by 1-way ANOVA (significant from other 2 groups). ***P < 0.001.

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