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, Guang Yao, Mark C. Leake, Chien Jung Lo, Fan Bai

Research output: Contribution to journalArticle

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 that 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.

LanguageEnglish (US)
Pages143-156
Number of pages14
JournalMolecular cell
Volume73
Issue number1
DOIs
StatePublished - Jan 3 2019

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Adenosine Triphosphate
Anti-Bacterial Agents
Proteins
Resuscitation
Cell Survival
Bacteria
Therapeutics

Keywords

  • ATP
  • bacterial antibiotic tolerance
  • cell resuscitation
  • DnaK-ClpB complex
  • dormancy depth
  • persisters
  • protein aggregates
  • viable but non-culturable cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

ATP-Dependent Dynamic Protein Aggregation Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance. / Pu, Yingying; Li, Yingxing; Jin, Xin; Tian, Tian; Ma, Qi; Zhao, Ziyi; Lin, Ssu Yuan; Chen, Zhanghua; Li, Binghui; Yao, Guang; Leake, Mark C.; Lo, Chien Jung; Bai, Fan.

In: Molecular cell, Vol. 73, No. 1, 03.01.2019, p. 143-156.

Research output: Contribution to journalArticle

Pu, Y, Li, Y, Jin, X, Tian, T, Ma, Q, Zhao, Z, Lin, SY, Chen, Z, Li, B, Yao, G, Leake, MC, Lo, CJ & Bai, F 2019, 'ATP-Dependent Dynamic Protein Aggregation Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance', Molecular cell, vol. 73, no. 1, pp. 143-156. https://doi.org/10.1016/j.molcel.2018.10.022
Pu, Yingying ; Li, Yingxing ; Jin, Xin ; Tian, Tian ; Ma, Qi ; Zhao, Ziyi ; Lin, Ssu Yuan ; Chen, Zhanghua ; Li, Binghui ; Yao, Guang ; Leake, Mark C. ; Lo, Chien Jung ; Bai, Fan. / ATP-Dependent Dynamic Protein Aggregation Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance. In: Molecular cell. 2019 ; Vol. 73, No. 1. pp. 143-156.
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