Cheverton, AM;
Gollan, B;
Przydacz, M;
Wong, CT;
Mylona, A;
Hare, SA;
Helaine, S;
(2016)
A Salmonella Toxin Promotes Persister Formation through Acetylation of tRNA.
Molecular Cell
, 63
(1)
pp. 86-96.
10.1016/j.molcel.2016.05.002.
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Abstract
The 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.
| Type: | Article |
|---|---|
| Title: | A Salmonella Toxin Promotes Persister Formation through Acetylation of tRNA |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.molcel.2016.05.002 |
| Publisher version: | https://doi.org/10.1016/j.molcel.2016.05.002 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, AMINOACYL-TRANSFER-RNA, BACTERIAL PERSISTENCE, STOCHASTIC INDUCTION, INHIBITS TRANSLATION, ANTITOXIN SYSTEMS, ESCHERICHIA-COLI, HYDROLASE, CELLS, COOPERATIVITY, ENDONUCLEASES |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10107614 |
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