title: Resveratrol induced inhibition of Escherichia coli proceeds via membrane oxidation and independent of diffusible reactive oxygen species generation.
abstract: Resveratrol (5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol), a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS) generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry) and propidium iodide uptake (flow cytometry and microscopy) as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event.
authors.affiliation: Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Subramanian
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Goswami
authors.affiliation: Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Narendra
authors.initials: N
authors.lastname: Jawali
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D013267:Stilbenes; D015534:Trans-Activators; D014157:Transcription Factors; C499299:oxyR protein, E coli; C070724:SoxR protein, Bacteria; C070725:SoxS protein, E coli; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000077185:Resveratrol
keywords: Adaptive response; Antibacterial; Antioxidant deficient mutants; Antioxidants