Modes of antibacterial action of curcumin under dark and light conditions: A toxicoproteomics approach.
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 (H2S and NH3) 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.



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.
Institute of Postharvest and Food Sciences, Agricultural Research Organization, The Volcani Center, Rishon LeZion 7528809, Israel; Institute of Biochemistry, Food Science and Nutrition, Hebrew University of Jerusalem, Rehovot 76100, Israel.
Ilya
I
Shlar
Institute of Postharvest and Food Sciences, Agricultural Research Organization, The Volcani Center, Rishon LeZion 7528809, Israel.
Samir
S
Droby
Institute of Postharvest and Food Sciences, Agricultural Research Organization, The Volcani Center, Rishon LeZion 7528809, Israel. Electronic address: vrodov@agri.gov.il.
Victor
V
Rodov
D000900:Anti-Bacterial Agents / Q000528:radiation effects* / Q000633:toxicity; D003474:Curcumin / Q000528:radiation effects* / Q000633:toxicity; D003623:Dark Adaptation; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008027:Light; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017440:Photoperiod; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species
D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D009243:NAD; D007501:Iron; D003474:Curcumin
Curcumin; Escherichia coli; Free intracellular iron; Iron-sulfur clusters; Oxidative stress; Toxicoproteomics