creators_name: Kumar, Vineet 
creators_name: Mishra , Rajesh Kumar 
creators_name: Ghose, Debarghya 
creators_name: Kalita, Arunima 
creators_name: Dhiman , Pulkit 
creators_name: Prakash, Anand 
creators_name: Thakur , Nirja 
creators_name: Mitra, Gopa 
creators_name: Chaudhari , Vinod D 
creators_name: Arora, Amit 
creators_name: Dutta, Dipak 
type: article
datestamp: 2022-07-22 05:43:24
lastmod: 2022-07-22 05:43:24
metadata_visibility: show
title: Free spermidine evokes superoxide radicals that manifest toxicity
ispublished: pub
subjects: QR
keywords: E. coli; Escherichia coli; SpeG; biochemistry; chemical biology; chromosomes; gene expression; iron metabolism; oxidative stress; spermidine toxicity; superoxide radical.
note: The copyright of this article belongs to eLife 
abstract: Spermidine and other polyamines alleviate oxidative stress, yet excess spermidine seems toxic to Escherichia coli unless it is neutralized by SpeG, an enzyme for the spermidine N-acetyl transferase function. Thus, wild-type E. coli can tolerate applied exogenous spermidine stress, but ΔspeG strain of E. coli fails to do that. Here, using different reactive oxygen species (ROS) probes and performing electron paramagnetic resonance spectroscopy, we provide evidence that although spermidine mitigates oxidative stress by lowering overall ROS levels, excess of it simultaneously triggers the production of superoxide radicals, thereby causing toxicity in the ΔspeG strain. Furthermore, performing microarray experiment and other biochemical assays, we show that the spermidine-induced superoxide anions affected redox balance and iron homeostasis. Finally, we demonstrate that while RNA-bound spermidine inhibits iron oxidation, free spermidine interacts and oxidizes the iron to evoke superoxide radicals directly. Therefore, we propose that the spermidine-induced superoxide generation is one of the major causes of spermidine toxicity in E. coli.
date: 2022-04-13
date_type: published
publication: eLife
publisher: eLife
refereed: TRUE
official_url: https://elifesciences.org/articles/77704#content
citation:   Kumar, Vineet  and Mishra , Rajesh Kumar  and Ghose, Debarghya  and Kalita, Arunima  and Dhiman , Pulkit  and Prakash, Anand  and Thakur , Nirja  and Mitra, Gopa  and Chaudhari , Vinod D  and Arora, Amit  and Dutta, Dipak   (2022) Free spermidine evokes superoxide radicals that manifest toxicity.  eLife.