Pu, Yingying, Li, Yingxing, Jin, Xin et al. (10 more authors) (2019) ATP-dependent dynamic protein aggregation regulates bacterial dormancy depth critical for antibiotic tolerance. Molecular Cell. 143-156.e4. ISSN 1097-2765
Abstract
Cell dormancy is a widespread mechanism used by bacteria to evade environmental threats including antibiotics. Here we monitored bacterial antibiotic tolerance and regrowth at the single-cell level and found that each individual survival cell shows different ‘dormancy depth’, which in return regulates the lag time for cell resuscitation after removal of antibiotic. We further established that protein aggresome - a collection of endogenous protein aggregates - is an important indicator of bacterial dormancy depth, whose formation is promoted by decreased cellular ATP level. For cells to leave the dormant state and resuscitate, clearance of protein aggresome and recovery of proteostasis are required. We revealed the ability to recruit functional DnaK-ClpB machineries, which facilitate protein disaggregation in an ATP-dependent manner, determines the lag time for bacterial regrowth. Better understanding of the key factors regulating bacterial regrowth after surviving antibiotic attack could lead to new therapeutic strategies for combating bacterial antibiotic tolerance.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Elsevier Inc. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. |
Keywords: | ATP,DnaK-ClpB complex,bacterial antibiotic tolerance,cell resuscitation,dormancy depth,persisters,protein aggregates,viable but non-culturable cells |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Physics (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 01 Nov 2018 09:40 |
Last Modified: | 16 Oct 2024 15:14 |
Published Version: | https://doi.org/10.1016/j.molcel.2018.10.022 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.molcel.2018.10.022 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138082 |
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