Modes of antibacterial action of curcumin under dark and light conditions: A toxicoproteomics approach.

Unlabelled: Curcumin is a potent natural food-grade antimicrobial compound. Exposure to light further enhances its antimicrobial capacity. Proteomic methods were used in this study for investigating the mechanistic aspects of the antibacterial curcumin effects in the dark and upon illumination. Escherichia coli cells exposed to water-dispersible curcumin-methyl-β-cyclodextrin inclusion complex under dark and light conditions were compared with the non-treated cells kept under the same illumination regimes. Curcumin treatment in the dark evoked adaptive responses aimed at mitigation of oxidative stress, DNA protection, proteostasis, modulation of redox state via changing NADH level, and gasotransmitter (HS and NH) biosynthesis. Although part of these phenomena were also present in E. coli treated under light, the light-induced curcumin toxicity was prevailed by maladaptive responses. The ROS burst induced upon curcumin treatment under light overrode the cellular adaptive mechanisms disrupting the iron metabolism, deregulating the iron-sulfur cluster biosynthesis and eventually leading to cell death. The toxicoproteomic findings were validated by transcriptomic analysis and by assessment of intracellular ROS, NADH, NADPH and iron levels.

Significance: The results of this study elucidate putative mechanistic basis of antibacterial effects of curcumin, suggesting ways towards more efficient contamination control. In particular, the antimicrobial efficacy of curcumin can be potentiated by targeting bacterial systems that remediate its dark toxicity by free radical detoxification and modulation of cell redox status. To the best of the authors' knowledge, this is the first proteomic study differentiating between the dark and light-induced antimicrobial activity of curcumin.