Mechanistic insights into HipA‐mediated bacterial persistence: Role of initial cellular states and toxin expression kinetics
4 affiliations
- 1School of Chemistry Northeast Normal University Changchun China
- 2State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun China
- 3School of Applied Chemistry and Engineering University of Science and Technology of China Hefei China
- 4Department of Chemistry and Physics State University of New York at Stony Brook Stony Brook New York USA
Abstract
Persistent bacteria subpopulations showing multidrug tolerance pose significant challenges to antibiotic therapy. While the HipBA toxin–antitoxin (TA) system is known to play a role in persister formation, existing studies predominantly focus on its kinase activity and intracellular regulatory pathways, with limited attention to the environmental or conditional factors. In this study, we administered controlled induction of HipA across varied growth conditions in Escherichia coli, establishing that conditional constraints fundamentally modulate HipA's capacity to induce persistence. We demonstrated that cells in the lag phase, rather than in the exponential or stationary phase, were more likely to enter the persistent state upon HipA upregulation. Moreover, our results indicated that the accumulation rate of HipA, rather than the absolute HipA level, was a crucial determinant of persister frequency. Finally, we confirmed the essential role of RelA in HipA‐mediated formation of persistent bacteria. These findings highlight the importance of previously unexplored conditional factors and expression kinetics in HipA‐mediated persistence, providing mechanistic insights that link toxin kinetics, growth phase regulation, and stringent response signaling in bacterial antibiotic tolerance.
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BibTeX
@article{zhao2026mechanistic,
title = {{Mechanistic insights into HipA‐mediated bacterial persistence: Role of initial cellular states and toxin expression kinetics}},
author = {Jing Zhao and Yixiao Xiong and Hongxia Zhao and Jin Wang and Xiaona Fang},
journal = {mLife},
year = {2026},
month = sep,
doi = {10.1002/mlf2.70095},
url = {https://doi.org/10.1002/mlf2.70095},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanistic insights into HipA‐mediated bacterial persistence: Role of initial cellular states and toxin expression kinetics
AU - Jing Zhao
AU - Yixiao Xiong
AU - Hongxia Zhao
AU - Jin Wang
AU - Xiaona Fang
PY - 2026
DA - 2026/09/16
JO - mLife
DO - 10.1002/mlf2.70095
UR - https://doi.org/10.1002/mlf2.70095
AB - Persistent bacteria subpopulations showing multidrug tolerance pose significant challenges to antibiotic therapy. While the HipBA toxin–antitoxin (TA) system is known to play a role in persister formation, existing studies predominantly focus on its kinase activity and intracellular regulatory pathways, with limited attention to the environmental or conditional factors. In this study, we administered controlled induction of HipA across varied growth conditions in Escherichia coli, establishing that conditional constraints fundamentally modulate HipA's capacity to induce persistence. We demonstrated that cells in the lag phase, rather than in the exponential or stationary phase, were more likely to enter the persistent state upon HipA upregulation. Moreover, our results indicated that the accumulation rate of HipA, rather than the absolute HipA level, was a crucial determinant of persister frequency. Finally, we confirmed the essential role of RelA in HipA‐mediated formation of persistent bacteria. These findings highlight the importance of previously unexplored conditional factors and expression kinetics in HipA‐mediated persistence, providing mechanistic insights that link toxin kinetics, growth phase regulation, and stringent response signaling in bacterial antibiotic tolerance.
SN - 2097-1699
SN - 2770-100X
ER -