BR-bodies facilitate adaptive responses and survival during copper stress in Caulobacter crescentus

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, ribonuclease E. First, biochemical assays and fluorescence microscopy experiments show that reduction of Cu²⁺ leads to cysteine oxidation, driving the transition of BR-bodies into more solid-like condensates. Second, tryptophan fluorescence and electron paramagnetic resonance assays reveal that ribonuclease E binds Cu²⁺ at histidine sites, creating a protective microenvironment that prevents mismetallation and preserves polynucleotide phosphorylase activity. In addition, we found that a substantial fraction of BR-bodies colocalizes with polyphosphate, which is also known to bind copper and facilitate the copper stress response. More broadly, this example illustrates how metal-condensate interactions can regulate the properties of condensate material and establish specialized chemical environments that protect enzyme function.