| Title: |
The metabolic slowdown caused by the deletion of pspA accelerates protein aggregation during stationary phase facilitating antibiotic persistence |
| Authors: |
Li, Yingxing; Chen, Xiao; Zhang, Weili; Fang, Kefan; Tian, Jingjing; Li, Fangyuan; Han, Mingfei; Huang, Jingjing; Sun, Tianshu; Bai, Fan; Cheng, Mei; Xu, Yingchun |
| Contributors: |
Silverman, Jared A.; MOST | National Natural Science Foundation of China; Special Foundation for National Science and Technology Basic Research Program of China; Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences |
| Source: |
Antimicrobial Agents and Chemotherapy ; volume 68, issue 2 ; ISSN 0066-4804 1098-6596 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2024 |
| Description: |
Entering a dormant state is a prevailing mechanism used by bacterial cells to transiently evade antibiotic attacks and become persisters. The dynamic progression of bacterial dormancy depths driven by protein aggregation has been found to be critical for antibiotic persistence in recent years. However, our current understanding of the endogenous genes that affects dormancy depth remains limited. Here, we discovered a novel role of phage shock protein A ( pspA ) gene in modulating bacterial dormancy depth. Deletion of pspA of Escherichia coli resulted in increased bacterial dormancy depths and prolonged lag times for resuscitation during the stationary phase. ∆pspA exhibited a higher persister ratio compared to the wild type when challenged with various antibiotics. Microscopic images revealed that ∆pspA showed accelerated formation of protein aggresomes, which were collections of endogenous protein aggregates. Time-lapse imaging established the positive correlation between protein aggregation and antibiotic persistence of ∆pspA at the single-cell level. To investigate the molecular mechanism underlying accelerated protein aggregation, we performed transcriptome profiling and found the increased abundance of chaperons and a general metabolic slowdown in the absence of pspA . Consistent with the transcriptomic results, the ∆pspA strain showed a decreased cellular ATP level, which could be rescued by glucose supplementation. Then, we verified that replenishment of cellular ATP levels by adding glucose could inhibit protein aggregation and reduce persister formation in ∆pspA . This study highlights the novel role of pspA in maintaining proteostasis, regulating dormancy depth, and affecting antibiotic persistence during stationary phase. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/aac.00937-23 |
| Availability: |
https://doi.org/10.1128/aac.00937-23; https://journals.asm.org/doi/pdf/10.1128/aac.00937-23 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.9FFE07F9 |
| Database: |
BASE |