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A Salmonella toxin promotes persister formation through acetylation of tRNA
journal contribution
posted on 2023-06-09, 08:01 authored by Angela M Cheverton, Bridget Gollan, Michael Przydacz, Chi T Wong, Anastasia Mylona, Stephen Hare, Sophie HelaineThe recalcitrance of many bacterial infections to antibiotic treatment is thought to be due to the presence of persisters that are non-growing, antibiotic-insensitive cells. Eventually, persisters resume growth, accounting for relapses of infection. Salmonella is an important pathogen that causes disease through its ability to survive inside macrophages. After macrophage phagocytosis, a significant proportion of the Salmonella population forms non-growing persisters through the action of toxin-antitoxin modules. Here we reveal that one such toxin, TacT, is an acetyltransferase that blocks the primary amine group of amino acids on charged tRNA molecules, thereby inhibiting translation and promoting persister formation. Furthermore, we report the crystal structure of TacT and note unique structural features, including two positively charged surface patches that are essential for toxicity. Finally, we identify a detoxifying mechanism in Salmonella wherein peptidyl-tRNA hydrolase counteracts TacT-dependent growth arrest, explaining how bacterial persisters can resume growth.
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Publication status
- Published
File Version
- Published version
Journal
Molecular CellISSN
1097-2765Publisher
ElsevierExternal DOI
Issue
1Volume
63Page range
86-96Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-09-21First Open Access (FOA) Date
2017-09-21First Compliant Deposit (FCD) Date
2017-09-21Usage metrics
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