A tripartite RpoS-CRP-cAMP-Cra circuit orchestrates metabolic reprogramming during stress adaptation
- 1Department of Pathogenic Biology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University , Nanjing, Jiangsu 210003 ,
- 2Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanology, Shenzhen University , Shenzhen, Guangdong 518060 ,
- 3School of Biomedical Sciences, Li KaShing Faculty of Medicine, Hong Kong University, Pokfulam, SAR , Hong Kong 999077 ,
Abstract
The alternative sigma factor RpoS (σS) governs stress adaptation in many bacterial clades, yet how it coordinates stress responses with metabolic demands remains poorly understood. Thus, by integrating RNA-seq, ChIP-seq, and physiological and molecular assays, we redefined the RpoS regulon in Escherichia coli, expanding it to 667 genes and demonstrating that metabolic genes unexpectedly predominate over stress-response targets. RpoS directly drives a massive metabolic reprogramming event: it activates glycolytic and sugar transport genes while simultaneously repressing the trichloroacetic acid cycle and oxidative phosphorylation. This metabolic pivot is finely tuned by a novel RpoS-CRP-cAMP-Cra tripartite circuit to balance energy efficiency with survival during stationary phase. Furthermore, we provide a mechanistic framework for RpoS-mediated bidirectional regulation rooted in σS-factor competition, where transcriptional efficiency in the absence of RpoS dictates the regulatory mode: highly efficient promoters are repressed by RpoS displacement, whereas weak promoters are activated. This study advances our understanding of transcriptional precision during bacterial adaptation and offers an architectural blueprint for synthetic metabolic engineering.
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BibTeX
@article{chen2026tripartite,
title = {{A tripartite RpoS-CRP-cAMP-Cra circuit orchestrates metabolic reprogramming during stress adaptation}},
author = {Wenbo Chen and Yong Feng and Lin Liu and Rao Ma and Antoine Danchin and Conghui You},
journal = {Nucleic Acids Research},
year = {2026},
month = oct,
doi = {10.1093/nar/gkag982},
url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag982/8915331},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - A tripartite RpoS-CRP-cAMP-Cra circuit orchestrates metabolic reprogramming during stress adaptation
AU - Wenbo Chen
AU - Yong Feng
AU - Lin Liu
AU - Rao Ma
AU - Antoine Danchin
AU - Conghui You
PY - 2026
DA - 2026/10/14
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag982
UR - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag982/8915331
AB - The alternative sigma factor RpoS (σS) governs stress adaptation in many bacterial clades, yet how it coordinates stress responses with metabolic demands remains poorly understood. Thus, by integrating RNA-seq, ChIP-seq, and physiological and molecular assays, we redefined the RpoS regulon in Escherichia coli, expanding it to 667 genes and demonstrating that metabolic genes unexpectedly predominate over stress-response targets. RpoS directly drives a massive metabolic reprogramming event: it activates glycolytic and sugar transport genes while simultaneously repressing the trichloroacetic acid cycle and oxidative phosphorylation. This metabolic pivot is finely tuned by a novel RpoS-CRP-cAMP-Cra tripartite circuit to balance energy efficiency with survival during stationary phase. Furthermore, we provide a mechanistic framework for RpoS-mediated bidirectional regulation rooted in σS-factor competition, where transcriptional efficiency in the absence of RpoS dictates the regulatory mode: highly efficient promoters are repressed by RpoS displacement, whereas weak promoters are activated. This study advances our understanding of transcriptional precision during bacterial adaptation and offers an architectural blueprint for synthetic metabolic engineering.
SN - 0305-1048
SN - 1362-4962
ER -