ATP-Dependent Dynamic Protein Aggregation Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance.

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ID: 67159
2019
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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.
Reference Key
pu2019atpdependentmolecular Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors 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;
Journal molecular cell
Year 2019
DOI
S1097-2765(18)30882-7
URL
Keywords
atp dnak-clpb complex bacterial antibiotic tolerance cell resuscitation dormancy depth persisters protein aggregates viable but non-culturable cells

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