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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 1

Catalase inactivation by CW and pulsed blue light in a wavelength-dependent manner.

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Catalase inactivation by CW and pulsed blue light in a wavelength-depend...
(A) P. aeruginosa catalase structure through PyMOL simulation. PDB 4E37. (B) Raman spectra of a bovine liver catalase film dried on a cover slide before (untreated) and after 410 nm light exposure. The Raman peak at 754 cm–1 is highlighted by an arrow. 410 nm: 50 mW/cm2, 10 minutes. SDs at each Raman shift are shaded. (C–E) Remaining catalase percentage of bovine liver catalase (C, 2.5 U/mL), stationary-phase MRSA USA300 (D), and stationary-phase P. aeruginosa PAO1 (E) under blue light exposure at different wavelengths. (F–H) Comparison of CW and ns-410 nm exposure on inhibiting bovine liver catalase (F, 4 U/mL), catalase from stationary-phase MRSA USA300 (G) and stationary-phase P. aeruginosa PAO1 (H). (I) Raman spectra of bovine liver catalase film dried on a cover slide under CW-410 and ns-410 exposure. Light: 50 mW/cm2, 5 minutes. Data: Mean + SD from 3 replicates for panels B–H. Statistical analysis was obtained through Student’s unpaired 2-tailed t test. ***P < 0.001.

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