Pressure-induced membrane tension mechanically opens the germinant receptor GerA ion channel to trigger bacterial spore germination
5 affiliations
- 1College of Food Science and Nutritional Engineering, China Agricultural University
- 2Center for High Pressure Science and Technology Advanced Research (HPSTAR)
- 3Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- 4Institute of Microbiology, Chinese Academy of Sciences
- 5Department of Molecular Biology and Biophysics, UConn Health
Abstract
High pressure (HP) can trigger bacterial spore germination, acting either through germinant receptors (GRs) or the SpoVA channel. However, the mechanism by which HP activates these membrane-embedded proteins remains elusive. Here, using Bacillus subtilis , we demonstrate that the GerA GR is the primary target of moderate HP (50–300 MPa). Mutagenesis reveals that pore-lining residues within the GerA ion channel are essential for the pressure response, whereas canonical ligand-binding and intramembrane signaling residues are dispensable. We then propose a s tretch- t o- o pen (STO) model, in which HP differentially compresses the more compliant inner membrane (IM) relative to the rigid spore core, generating lateral membrane tension that promotes the opening of the GerA channel. In situ membrane tension measurements indicate HP-induced compression of IM phospholipids and elevated membrane tension. This tension-dependent gating is further supported by the pressure-dependent phenotypic rescue of GerA channel mutants. Consistently, HP increases IM permeability to water-soluble and membrane-impermeable agents (propidium iodide and formaldehyde), an effect potentiated by GerA, indicating concomitant opening of GerA by HP. Furthermore, modulating IM fluidity via heat activation or decoating altered membrane physical properties and delayed HP-induced germination, establishing the IM as the critical mechanical transducer. Additionally, computational modeling and calculations support faster compression of the IM than of the core under HP, rationalizing the source of tensile stress. Together, our findings establish a novel mechanism of HP-induced GerA activation via the STO model: HP compresses the IM, generates lateral tension, and promotes opening of the GerA ion channel to trigger bacterial spore germination.
IMPORTANCE: Bacterial spores are notoriously resilient, posing significant challenges to health and industry. While high pressure is known to trigger spore germination, the biophysical mechanism has remained elusive. Here, we provide evidence that high pressure mechanically activates the germinant receptor GerA via a “stretch-to-open” mechanism. Because the inner membrane is highly compressible compared to the rigid spore core, pressure induces membrane compression that generates lateral tension. This tension promotes opening of the GerA ion channel. Our study identifies the inner membrane as a critical mechanical transducer, addressing a long-standing question in spore biology and suggesting a distinct mechanosensory adaptation involved in spore revival.
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BibTeX
@article{rao2026pressureinduced,
title = {{Pressure-induced membrane tension mechanically opens the germinant receptor GerA ion channel to trigger bacterial spore germination}},
author = {Lei Rao and Tianyu Zhang and Ziqi Gong and Ke Liu and Yonggang Wang and Bing Zhou and Yongqiang Gao and Peter Setlow and Xiaojun Liao},
journal = {mBio},
year = {2026},
month = oct,
doi = {10.1128/mbio.02008-26},
url = {https://journals.asm.org/doi/10.1128/mbio.02008-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pressure-induced membrane tension mechanically opens the germinant receptor GerA ion channel to trigger bacterial spore germination
AU - Lei Rao
AU - Tianyu Zhang
AU - Ziqi Gong
AU - Ke Liu
AU - Yonggang Wang
AU - Bing Zhou
AU - Yongqiang Gao
AU - Peter Setlow
AU - Xiaojun Liao
PY - 2026
DA - 2026/10/30
JO - mBio
DO - 10.1128/mbio.02008-26
UR - https://journals.asm.org/doi/10.1128/mbio.02008-26
AB - High pressure (HP) can trigger bacterial spore germination, acting either through germinant receptors (GRs) or the SpoVA channel. However, the mechanism by which HP activates these membrane-embedded proteins remains elusive. Here, using Bacillus subtilis , we demonstrate that the GerA GR is the primary target of moderate HP (50–300 MPa). Mutagenesis reveals that pore-lining residues within the GerA ion channel are essential for the pressure response, whereas canonical ligand-binding and intramembrane signaling residues are dispensable. We then propose a s tretch- t o- o pen (STO) model, in which HP differentially compresses the more compliant inner membrane (IM) relative to the rigid spore core, generating lateral membrane tension that promotes the opening of the GerA channel. In situ membrane tension measurements indicate HP-induced compression of IM phospholipids and elevated membrane tension. This tension-dependent gating is further supported by the pressure-dependent phenotypic rescue of GerA channel mutants. Consistently, HP increases IM permeability to water-soluble and membrane-impermeable agents (propidium iodide and formaldehyde), an effect potentiated by GerA, indicating concomitant opening of GerA by HP. Furthermore, modulating IM fluidity via heat activation or decoating altered membrane physical properties and delayed HP-induced germination, establishing the IM as the critical mechanical transducer. Additionally, computational modeling and calculations support faster compression of the IM than of the core under HP, rationalizing the source of tensile stress. Together, our findings establish a novel mechanism of HP-induced GerA activation via the STO model: HP compresses the IM, generates lateral tension, and promotes opening of the GerA ion channel to trigger bacterial spore germination. IMPORTANCE: Bacterial spores are notoriously resilient, posing significant challenges to health and industry. While high pressure is known to trigger spore germination, the biophysical mechanism has remained elusive. Here, we provide evidence that high pressure mechanically activates the germinant receptor GerA via a “stretch-to-open” mechanism. Because the inner membrane is highly compressible compared to the rigid spore core, pressure induces membrane compression that generates lateral tension. This tension promotes opening of the GerA ion channel. Our study identifies the inner membrane as a critical mechanical transducer, addressing a long-standing question in spore biology and suggesting a distinct mechanosensory adaptation involved in spore revival.
SN - 2150-7511
ER -