# DEAD-box ATPase–marked condensates coordinate compartmentalized translation and antibiotic persistence

## TL;DR

This study shows how protein condensates help bacteria become dormant and tolerate antibiotics by silencing local protein production.

## Contribution

The study reveals a novel mechanism where DEAD-box ATPase-associated condensates coordinate dormancy and antibiotic persistence in bacteria.

## Key findings

- Mutations in serS or SHX treatment cause SerRS to be sequestered into DEAD-box ATPase-associated condensates.
- Condensates silence local translation, leading to bacterial dormancy and antibiotic tolerance.
- These findings suggest condensates could be targeted to combat antibiotic tolerance.

## Abstract

Antibiotic-tolerant persisters use dormancy as a bet-hedging strategy to evade lethal antibiotics, undermining therapeutic efficacy. Protein condensates have been implicated in bacterial dormancy, yet how these assemblies orchestrate dormancy entry remains unclear. We evolved persisters that enter dormancy before the stationary phase, most harboring mutations in serS, encoding seryl-transfer RNA synthetase (SerRS). These variants recapitulated persistence induced by serine hydroxamate (SHX), a serine analog and SerRS inhibitor. Both the serS mutation and SHX treatment trigger SerRS sequestration into conserved DEAD-box adenosine triphosphatase–associated condensates, coinciding with growth arrest and dormancy. In vitro, the SerRS variant preferentially partitions into DeaD granules, consistent with its distinct in vivo localization. Microscopy revealed spatially restricted translation silencing within condensates upon SerRS partitioning. Together, these phase-separated condensates act as hubs that coordinate the transition from proliferation to dormancy, paralleling eukaryotic cell fate control via localized translation. Our findings provide mechanistic insight into bacterial persistence and suggest that targeting condensates could help combat antibiotic tolerance and delay resistance.

Sequestration of SerRS into condensates silences local translation, promoting bacterial dormancy and antibiotic tolerance.