Global proteolysis during starvation governs proteome remodeling and a survival-regrowth trade-off in bacteria.
4 affiliations
- 1Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093.
- 2Department of Physics, University of California at San Diego, La Jolla, CA 92093.
- 3Department of Mathematics, University of California at San Diego, La Jolla, CA 92093.
- 4Bavarian Center for Biomolecular Mass Spectrometry, School of Life Sciences, Technical University of Munich, Freising, Germany.
Abstract
Starving bacteria must synthesize stress proteins to survive, but how protein synthesis persists in the absence of nutrient influx is unclear. We show that in Escherichia coli, carbon starvation triggers large-scale proteome remodeling, with global proteolysis supplying both the amino acids (AAs) and ATP for protein synthesis. This remodeling occurs in two phases, with a short preparatory phase relying on constitutive proteolytic machinery and fueled by residual carbon waste, and a more extended phase, relying on starvation-induced protein components synthesized during the preparatory phase and fueled by AA catabolism. The starvation-induced protein degradation (SPD) program dominating the extended phase depends on YeaG, a little-known, broadly conserved protein highly expressed in stationary phase under the control of the general stress sigma factor RpoS. SPD fuels the synthesis of stress proteins, including those in the RpoS regulon and AA catabolic enzymes, markedly enhancing survival and accounting for much of the viability benefit conferred by RpoS during carbon starvation. However, in mutants where an energy source can be supplemented without enabling biomass growth, SPD and the accompanying protein synthesis are largely dispensable for survival, indicating that a primary physiological function of the synthesized stress proteins is to conserve or recycle energy during carbon starvation. Because SPD targets biosynthetic enzymes nonspecifically, proteome remodeling via SPD imposes a fundamental trade-off between long-term survival and short-term metabolic activity, manifested as a lag before regrowth upon nutrient replenishment. Together, these findings establish SPD as a general physiological strategy shaping protein synthesis and survival in nongrowing bacteria.
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BibTeX
@article{manzanarez2026global,
title = {{Global proteolysis during starvation governs proteome remodeling and a survival-regrowth trade-off in bacteria.}},
author = {Gabriel Manzanarez and Rohan Balakrishnan and Harish Kannan and Miriam Abele and Hiroyuki Okano and Fukang She and Zhongge Zhang and Chenhao Wu and Lance Freiman and Christina Ludwig and Matteo Mori and Terence Hwa},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2611560123},
url = {https://europepmc.org/article/MED/42879477},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Global proteolysis during starvation governs proteome remodeling and a survival-regrowth trade-off in bacteria.
AU - Gabriel Manzanarez
AU - Rohan Balakrishnan
AU - Harish Kannan
AU - Miriam Abele
AU - Hiroyuki Okano
AU - Fukang She
AU - Zhongge Zhang
AU - Chenhao Wu
AU - Lance Freiman
AU - Christina Ludwig
AU - Matteo Mori
AU - Terence Hwa
PY - 2026
DA - 2026/10/15
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2611560123
UR - https://europepmc.org/article/MED/42879477
AB - Starving bacteria must synthesize stress proteins to survive, but how protein synthesis persists in the absence of nutrient influx is unclear. We show that in Escherichia coli, carbon starvation triggers large-scale proteome remodeling, with global proteolysis supplying both the amino acids (AAs) and ATP for protein synthesis. This remodeling occurs in two phases, with a short preparatory phase relying on constitutive proteolytic machinery and fueled by residual carbon waste, and a more extended phase, relying on starvation-induced protein components synthesized during the preparatory phase and fueled by AA catabolism. The starvation-induced protein degradation (SPD) program dominating the extended phase depends on YeaG, a little-known, broadly conserved protein highly expressed in stationary phase under the control of the general stress sigma factor RpoS. SPD fuels the synthesis of stress proteins, including those in the RpoS regulon and AA catabolic enzymes, markedly enhancing survival and accounting for much of the viability benefit conferred by RpoS during carbon starvation. However, in mutants where an energy source can be supplemented without enabling biomass growth, SPD and the accompanying protein synthesis are largely dispensable for survival, indicating that a primary physiological function of the synthesized stress proteins is to conserve or recycle energy during carbon starvation. Because SPD targets biosynthetic enzymes nonspecifically, proteome remodeling via SPD imposes a fundamental trade-off between long-term survival and short-term metabolic activity, manifested as a lag before regrowth upon nutrient replenishment. Together, these findings establish SPD as a general physiological strategy shaping protein synthesis and survival in nongrowing bacteria.
SN - 0027-8424
SN - 1091-6490
ER -