# Characterization of Tellurite Toxicity to Escherichia coli Under Aerobic and Anaerobic Conditions

## TL;DR

This study explores how tellurite affects Escherichia coli under both oxygen-rich and oxygen-free conditions, revealing new insights into its toxicity beyond oxidative stress.

## Contribution

The study identifies novel non-ROS mechanisms of tellurite toxicity, including effects on amino acid metabolism and membrane lipid changes.

## Key findings

- Tellurite disrupts amino acid and nucleotide metabolism, impairing protein synthesis in E. coli.
- Tellurite alters membrane lipid composition, particularly phosphatidylethanolamine derivatives, which may influence membrane properties.
- Anaerobic conditions increase E. coli's tellurite tolerance, suggesting ROS-independent resistance mechanisms.

## Abstract

Tellurite (TeO32−) is a highly soluble and toxic oxyanion that inhibits the growth of Escherichia coli at concentrations as low as ~1 µg/mL. This toxicity has been primarily attributed to the generation of reactive oxygen species (ROS) during its intracellular reduction by thiol-containing molecules and NAD(P)H-dependent enzymes. However, under anaerobic conditions, E. coli exhibits significantly increased tellurite tolerance—up to 100-fold in minimal media—suggesting the involvement of additional, ROS-independent mechanisms. In this study, we combined chemical-genomic screening, untargeted metabolomics, and targeted biochemical assays to investigate the effects of tellurite under both aerobic and anaerobic conditions. Our findings reveal that tellurite perturbs amino acid and nucleotide metabolism, leading to intracellular imbalances that impair protein synthesis. Additionally, tellurite induces notable changes in membrane lipid composition, particularly in phosphatidylethanolamine derivatives, which may influence biophysical properties of the membrane, such as fluidity or curvature. This membrane remodeling could contribute to the increased resistance observed under anaerobic conditions, although direct evidence of altered membrane fluidity remains to be established. Overall, these results demonstrate that tellurite toxicity extends beyond oxidative stress, impacting central metabolic pathways and membrane-associated functions regardless of oxygen availability.