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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 7

Photoinactivation of catalase reduces P. aeruginosa burden in a P. aeruginosa–induced mouse skin abrasion model.

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Photoinactivation of catalase reduces P. aeruginosa burden in a P. aerug...
(A) Schematic illustration of in vivo mouse experiment. (B) CFU/mL of P. aeruginosa PAO1 from the infected wound tissues among 4 different groups. (C and D) Histology analysis of mouse skin from untreated group along with 410 nm plus H2O2 treated group. Scale bar: 100 μm. Data: Mean ± SD from at least 6 replicates (n = 3–4 mice/group, 6–8 infected area/group). 410 nm: 120 J/cm2. H2O2: 0.5%. Significant difference was determined by Student’s 2-tailed unpaired t test and 1-way ANOVA. ***P < 0.001, *P < 0.05. An outlier was removed based on Dixon’s Q test and the box-and-whisker plot.

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