The Contribution of Superoxide Radical to Cadmium Toxicity in E. coli

Abstract

Numerous reports suggest the involvement of oxidative stress in cadmium toxicity, but the nature of the reactive species and the mechanism of Cd-induced oxidative damage are not clear. In this study, E. coli mutants were used to investigate mechanisms of Cd toxicity. Effects of Cd on metabolic activity, production of superoxide radical by the respiratory chain, and induction of enzymes controlled by the soxRS regulon were investigated. In E. coli, the soxRS regulon controls defense against O·and univalent oxidants. Suppression of metabolic activity, inability of E. coli to adapt to new environment, and slow cell division were among the manifestations of Cd toxicity. Cd increased production of O· by the electron transport chain and prevented the induction of soxRS-controlled protective enzymes, even when the regulon was induced by the redox-cycling agent, paraquat. The effect was not limited to soxRS-dependent proteins and can be attributed to previously reported suppression of protein synthesis by Cd. Increased production of superoxide, combined with inability to express protective enzymes and to replace damaged proteins by de novo protein synthesis, seems to be the main reason for growth stasis and cell death in Cd poisoning.

Peer Review #2 of "Metal complexation by histidine-rich peptides confers protective roles against cadmium stress in Escherichia coli as revealed by proteomics analysis (v0.1)"

“…In normal condition, Cd 2+ is taken up by E. coli cells by an active transport system, in particular Mn 2+ uptake system (Laddaga & Silver 1985). Inside the cells, Cd 2+ induces cell damage by generation of reactive oxygen species (ROS) through the electron transport chain (Pacheco et al 2008;Thomas & Benov 2018). The presence of superoxide radical (O 2 .-) subsequently triggers the SoxRS regulon and results in the increased expression of antioxidative enzymes, mainly superoxide dismutase to protect the cells from cadmium stress (Geslin et al 2001).…”

“…Manuscript to be reviewed dysfunction, and imbalance of oxidative pressure leading to growth retardation were reported (Hossain et al 2012). Induction of oxidative damage by superoxide radical together with inability to express protective enzymes and to replace damaged proteins by de novo protein synthesis have currently been reported to be the main reason for growth stasis and cell death in Cd poisoning (Thomas & Benov 2018). (ii) Cellular responses and adaptation: To reduce the toxic effects of cadmium ions, efflux system has not much been accepted as the primary defense mechanism of E. coli.…”

“…Results revealed that some regulatory systems, e.g. OxyR, SoxRS, RpoH, UspA, GrpE, RecA, and YodA, participated in the cadmium stress (Ferianc et al 1998;LaRossa et al 1995;Lim et al 2009;Puskárová et al 2002;Shapiro & Keasling 1996;Thomas & Benov 2018;Van Dyk et al 1995). These inducible regulators can be classified in various groups as general stress regulons (UspA, YodA), SOS regulons (RecA), oxidative stress regulons (Oxy R, SoxRS), heat shock protein regulons (RpoH) and chaperones (GrpE) (Han & Lee 2006).…”

Metal complexation by histidine-rich peptides confers protective roles against cadmium stress inEscherichia colias revealed by proteomics analysis

“…Other toxic effects including disturbation of the cell division as a consequence of improper Z-ring formation, metabolic dysfunction, and imbalance of oxidative pressure leading to growth retardation were reported ( Hossain, Mallick & Mukherjee, 2012 ). Induction of oxidative damage by superoxide radical together with inability to express protective enzymes and to replace damaged proteins by de novo protein synthesis have currently been reported to be the main reason for growth stasis and cell death in Cd poisoning ( Thomas & Benov, 2018 ). (ii) Cellular responses and adaptation: the efflux system not been widely accepted as the primary defense mechanism of E. coli to reduce the toxic effects of cadmium ions.…”

“…Currently, regulation of the CDPs together with the other general stress responses was subsequently studied either at the transcriptional or translational levels by gene-array technology or two-dimensional gel electrophoresis ( Brocklehurst & Morby, 2000 ; Ferianc, Farewell & Nyström, 1998 ; Isarankura-Na-Ayudhya et al, 2009 ; Lausova, Ferianc & Polek, 1999 ). Results revealed that some regulatory systems, e.g., OxyR, SoxRS, RpoH, UspA, GrpE, RecA, and YodA, participated in the cadmium stress ( Ferianc, Farewell & Nyström, 1998 ; LaRossa, Smulski & Van Dyk, 1995 ; Lim et al, 2009 ; Puskárová et al, 2002 ; Shapiro & Keasling, 1996 ; Thomas & Benov, 2018 ; Van Dyk et al, 1995 ). These inducible regulators can be classified in various groups as general stress regulons (UspA, YodA), SOS regulons (RecA), oxidative stress regulons (OxyR, SoxRS), heat shock protein regulons (RpoH) and chaperones (GrpE) ( Han & Lee, 2006 ).…”