Description
The ResTA module (STM14_5441 – STM14_5442) is a type II toxin–antitoxin system composed of the RNase toxin ResT and the antitoxin ResA, implicated in bacterial persistence under antibiotic stress. Here, we report crystal structures of the Salmonella Typhimurium ResTA complex and characterize the molecular function of ResT as a ribosome-dependent RNase. Structural analysis and mutational studies identified key residues required for 30S ribosome binding and toxin activity. Functional assays demonstrated that ResT selectively promotes recovery after aminoglycoside treatment without increasing intrinsic antibiotic resistance. Transcriptomic and biochemical analyses revealed that ResT induction leads to intracellular ATP accumulation through suppression of ATP-consuming pathways and modulation of energy metabolism. Based on these findings, we propose a mechanism in which ResT-mediated ribosome inhibition enables aminoglycoside-specific persister formation via ATP reprogramming.
| I am the presenting author | Yes |
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