BR-Bodies Facilitate Adaptive Responses and Survival During Copper Stress in Caulobacter crescentus

Abstract

Microbes must rapidly adapt to environmental stresses, including toxic heavy metals like copper, by sensing and mitigating their harmful effects. Here, we demonstrate that the phase separation properties of bacterial ribonucleoprotein bodies (BR-bodies) enhance Caulobacter crescentus fitness under copper stress. To uncover the underlying mechanism, we identified two key interactions between copper and the central scaffold of BR-bodies, RNase E. First, biochemical assays and fluorescence microscopy experiments show that reductive chelation of Cu²⁺ leads to cysteine oxidation, driving the transition of BR-bodies into more solid-like condensates. Second, tryptophan fluorescence and EPR assays reveal that RNase E binds Cu²⁺ at histidine sites, creating a protective microenvironment that prevents mismetallation and preserves PNPase activity. More broadly, this example highlights how metal-condensate interactions can regulate condensate material properties and establish specialized chemical environments that safeguard enzyme function.