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    A Salmonella toxin promotes persister formation through acetylation of tRNA

    Cheverton, A.M. and Gollan, B. and Przydacz, M. and Wong, C.T. and Mylona, Anastasia and Hare, S.A. and Helaine, S. (2016) A Salmonella toxin promotes persister formation through acetylation of tRNA. Molecular Cell 63 (1), pp. 86-96. ISSN 1097-2765.

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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.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 13 Nov 2018 14:44
    Last Modified: 28 Jul 2019 13:47
    URI: http://eprints.bbk.ac.uk/id/eprint/25122

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