ATP-dependent dynamic protein aggregation regulates bacterial dormancy depth critical for antibiotic tolerance

Yingying Pu, Yingxing Li, Xin Jin, Tian Tian, Qi Ma, Ziyi Zhao, Ssu-yuan Lin, Zhanghua Chen, Binghui Li, Gung Yao, Mark Christian Leake, Chien-Jung Lo, Fan Bai

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)143-156.e4
Number of pages18
JournalMolecular Cell
Volume73
Issue number1
DOIs
Publication statusPublished - 3 Jan 2019

Bibliographical note

© 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

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