Epigallocatechin Gallate-Mediated Cell Death Is Triggered by Accumulation of Reactive Oxygen Species Induced via the Cpx Two-Component System in Escherichia coli

Abstract

The high antimicrobial activity of epigallocatechin gallate (EGCG), the most bioactive component of tea polyphenol with a number of health benefits, is well-known. However, little is known about the mechanism involved. Here, we discovered the relationship between reactive oxygen species (ROS), the Cpx system, and EGCG-mediated cell death. We first found an increase in ampicillin resistance as well as the transcription level of a LD-transpeptidase (LD-TPase) involved in cell wall synthesis; ycbB transcription was upregulated whereas that of another LD-TPase, ynhG, appeared to be constant after a short exposure of Escherichia coli to sub-inhibitory doses of EGCG. Additionally, the transcription level of cpxP, a downstream gene belonging to the Cpx regulon, was positively correlated with the concentration of EGCG, and significant upregulation was detected when cells were treated with high doses of EGCG. Through analysis of a cpxR deletion strain (ΔcpxR), we identified a constant ROS level and a notable increase in the survival rate of ΔcpxR, while the ROS level increased and the survival rate decreased remarkably in the wild-type strain. Furthermore, thiourea, which is an antioxidant, reduced the ROS level and antimicrobial activity of EGCG. Taken together, these results suggest that EGCG induces ROS formation by activating the Cpx system and mediates cell death.

Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect

“…The Cpx system is thought to control protein homeostasis in the cell envelope. When E. coli was exposed to EGCG, apoptosis happened because of ROS formation by the Cpx system [ 62 ]. RpoS is a general stress regulator in response to oxidative stress.…”

Protein-directed synthesis of ZIF-8 functionalized with a polymer as core–shell drug coatings with antibacterial and anti-inflammatory properties

“…44 Similarly, EGCG reportedly affects the multidrug efflux pump system of E. coli , inducing ROS formation by Cpx system activation and cell death. 45…”

“…44 Similarly, EGCG reportedly affects the multidrug efflux pump system of E. coli, inducing ROS formation by Cpx system activation and cell death. 45 In addition, the ROS generation at the surface of the bacteria could result in cell membrane damage. Thus, next, we quantified the lipid peroxidation in E. coli and S. aureus bacteria due to the exposure to EGCG-loaded POL@LZIF-8 nanocomposites.…”

Current understanding on antibacterial mechanisms and research progress of tea polyphenols as a supplementary disinfectant for drinking water

“…The differences between the two studies may be due to differences in strains, media, or EGCG concentrations, and further research is needed. In order to further explore the mechanism of EGCG-induced endogenous oxidative stress, Nie et al (2018) treated cpxRdeficient E. coli strains and common wild-type strains with EGCG and found that the cpxR-deficient strains had stable ROS and increased survival, while wild-type strains had elevated ROS levels and decreased survival. It is speculated that EGCG may interact with bacterial peptidoglycan and outer membrane proteins to induce cell envelope disorder.…”