Altered redox status, DNA damage and modulation of L-tryptophan metabolism contribute to antimicrobial action of curcumin

Abstract

Identification and development of newer and better antimicrobials from natural products represent ongoing research efforts by many investigators. Curcumin is a polyphenol commonly found in the plant Curcuma longa (better known as turmeric). It has been reported to possess several bioactivities including antioxidant, anti-cancer, anti-inflammatory, anti-diabetic, anti-fibrotic, and antimicrobial properties. However, little is known about the antimicrobial mode of action of curcumin, thus undermining its prospects as an alternative antimicrobial agent. In this study, we investigated the mechanism of antimicrobial action by curcumin. The mechanism of inhibition was evaluated in representatives of Gram negative (Escherichia coli) and Gram positive (Staphylococcus aureus) bacteria isolates, treated with either curcumin singly or in combination with ascorbic acid (1000 μg/mL). Results showed that curcumin has broad antimicrobial capacity. In addition, curcumin only and/or co-treatment with ascorbic acid caused lipid peroxidation in S. aureus and E. coli, and by extension led to DNA damage, indicative of oxidative stress. It is plausible that the oxidative might be related to the activation of the kynurenine pathway in S. aureus but not in E. coli. Furthermore, curcumin exposure led to elevated total antioxidant capacity (TAC) and level of total thiol, but decreased nitric oxide level in the bacteria isolates. Together, the findings suggest that oxidative stress and DNA damage might be partly responsible for the antimicrobial action of curcumin.

Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway

“…Stock cultures of selected Gram-positive and negative bacterial isolates were generated as reported elsewhere [ 16 , 17 ]. The purity of the strains was determined by streaking on nutrient agar plates that were incubated at 37 °C for 24 h. Only plates that showed pure colonies were sub-cultured and used for further studies.…”

“…The agar diffusion method, as previously described [ 16 , 17 ], was used. In this assay, nutrient agar was prepared into 100 mL capacity conical flask with 50 mL nutrient medium, as outlined by the manufacturer.…”

“…DMSO alone was used as the control. The zone of clearance was measured using a metric ruler as previously described [ 16 , 17 ].…”

“…All treated cells were incubated at 37 °C for 24 h and harvested by centrifugation [ 16 , 17 , 18 ]. The pellet was rinsed three times with physiological saline, re-suspended, homogenized, and used for biochemical studies.…”

Recent progress of bacterial FtsZ inhibitors with a focus on peptides

“…Lee et al investigated the novel antibacterial mechanism of curcumin against E. coli and found that curcumin could induce a bacterial apoptosis‐like response by reactive oxygen species (ROS) production, membrane depolarization, and Ca 2+ influx [98]. Curcumin alone or in combination with ascorbic acid led to lipid peroxidation and DNA damage in S. aureus and E. coli , suggesting that oxidative stress and DNA damage might be partly responsible for the antibacterial mechanism of curcumin [99]. Moreover, a carbocyclic curcumin analogue 2d had potent antibacterial activity against B. subtilis and MRSA; 2d inhibited the proliferation of B. subtilis by targeting FtsZ, destroyed the Z‐ring formation in bacteria within 5 min, and enhanced the GTPase activity of FtsZ [100].…”