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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 2

Photoinactivation of catalase effectively sensitizes pathogenic bacteria to H2O2.

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Photoinactivation of catalase effectively sensitizes pathogenic bacteria...
(A) CFU/mL of stationary-phase MRSA USA300 under various treatments. Dose: 50 mW/cm2, 5 minutes. H2O2: 22 mM, 30-minute incubation time. (B) CFU/mL of stationary-phase P. aeruginosa PAO1 under various treatments. Dose: 50 mW/cm2, 5 minutes. H2O2: 22 mM, 30-minute incubation time. (C–E) Time-killing curves of wild-type E. coli BW25113 (C), E. coli ΔkatG (D), and E. coli ΔkatGE (E) under different treatment schemes. ns-410 nm: 30 mW, 8 minutes, 14 J/cm2. (F) CFU plates of S. aureus Newman along with its isogenic catalase-mutant S. aureus ΔkatA with/without H2O2 treatment. (G and H) CFU/mL of S. aureus Newman (G) and S. aureus ΔkatA (H) under different treatment schemes. (I–L) Viable E. coli BW25113 (I and J) and E. coli ΔkatGE:pBad_katE (K and L) were enumerated after incubating with/without H2O2 (2.2 mM) for 30 minutes in the absence/presence of arabinose (4 hours) after 3 J/cm2 410 nm treatment. Data: Mean + SD from at least 3 biological replicates for all panels. Pound sign indicates the CFU results are below the detection limit. Statistical analysis was obtained by Student’s 2-tailed unpaired t test (compared with the untreated group) and 1-way ANOVA. *P < 0.05.

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