New insights into the disulfide stress response by the Bacillus subtilis Spx system at a single-cell level
Matavacas, Judith LU ; Anand, Deepak LU
and von Wachenfeldt, Claes
LU
(2023)
In Molecular Microbiology
120(1).
p.75-90
- Abstract
Spx is a global transcriptional regulator that orchestrates the Bacillus subtilis response to disulfide stress. The YjbH (SpxH) protein adapts Spx for ClpXP-mediated degradation, playing a critical role in the regulation of the cellular Spx levels. Upon stress, YjbH forms aggregates by a yet unknown mechanism, resulting in increased Spx levels due to reduced proteolysis. Here, we studied how individual cells use the Spx-YjbH system to respond to disulfide stress. We show, using fluorescent reporters, a correlation between the Spx levels and the amount of YjbH, as well as a transient growth inhibition upon disulfide stress. The in vivo dynamics and inheritance of YjbH aggregates are characterized by a bipolar distribution over time and... (More)
Spx is a global transcriptional regulator that orchestrates the Bacillus subtilis response to disulfide stress. The YjbH (SpxH) protein adapts Spx for ClpXP-mediated degradation, playing a critical role in the regulation of the cellular Spx levels. Upon stress, YjbH forms aggregates by a yet unknown mechanism, resulting in increased Spx levels due to reduced proteolysis. Here, we studied how individual cells use the Spx-YjbH system to respond to disulfide stress. We show, using fluorescent reporters, a correlation between the Spx levels and the amount of YjbH, as well as a transient growth inhibition upon disulfide stress. The in vivo dynamics and inheritance of YjbH aggregates are characterized by a bipolar distribution over time and appear to be entropy-driven by nucleoid exclusion. Moreover, we reveal that the population following disulfide stress is highly heterogenous in terms of aggregate load and that the aggregate load has strong implications for cellular fitness. We propose that the observed heterogeneity could be a mechanism to ensure population survival during stress. Finally, we find that the two YjbH domains (DsbA-like domain and winged-helix domain) contribute to its aggregation function, and show that the aggregation of the DsbA-like domain is conserved among other studied orthologs, whereas important differences are observed for the winged-helix domain.
(Less)
- author
- Matavacas, Judith
LU
; Anand, Deepak
LU
and von Wachenfeldt, Claes
LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bacillus subtilis, disulfide stress, protein aggregation, Spx, SpxH, YjbH
- in
- Molecular Microbiology
- volume
- 120
- issue
- 1
- pages
- 75 - 90
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:37330636
- scopus:85162264143
- ISSN
- 0950-382X
- DOI
- 10.1111/mmi.15108
- language
- English
- LU publication?
- yes
- id
- 1c169e80-f085-443b-85aa-5cc15b00747a
- date added to LUP
- 2023-09-15 09:35:25
- date last changed
- 2024-04-20 03:18:00
@article{1c169e80-f085-443b-85aa-5cc15b00747a,
abstract = {{<p>Spx is a global transcriptional regulator that orchestrates the Bacillus subtilis response to disulfide stress. The YjbH (SpxH) protein adapts Spx for ClpXP-mediated degradation, playing a critical role in the regulation of the cellular Spx levels. Upon stress, YjbH forms aggregates by a yet unknown mechanism, resulting in increased Spx levels due to reduced proteolysis. Here, we studied how individual cells use the Spx-YjbH system to respond to disulfide stress. We show, using fluorescent reporters, a correlation between the Spx levels and the amount of YjbH, as well as a transient growth inhibition upon disulfide stress. The in vivo dynamics and inheritance of YjbH aggregates are characterized by a bipolar distribution over time and appear to be entropy-driven by nucleoid exclusion. Moreover, we reveal that the population following disulfide stress is highly heterogenous in terms of aggregate load and that the aggregate load has strong implications for cellular fitness. We propose that the observed heterogeneity could be a mechanism to ensure population survival during stress. Finally, we find that the two YjbH domains (DsbA-like domain and winged-helix domain) contribute to its aggregation function, and show that the aggregation of the DsbA-like domain is conserved among other studied orthologs, whereas important differences are observed for the winged-helix domain.</p>}},
author = {{Matavacas, Judith and Anand, Deepak and von Wachenfeldt, Claes}},
issn = {{0950-382X}},
keywords = {{Bacillus subtilis; disulfide stress; protein aggregation; Spx; SpxH; YjbH}},
language = {{eng}},
number = {{1}},
pages = {{75--90}},
publisher = {{Wiley-Blackwell}},
series = {{Molecular Microbiology}},
title = {{New insights into the disulfide stress response by the Bacillus subtilis Spx system at a single-cell level}},
url = {{http://dx.doi.org/10.1111/mmi.15108}},
doi = {{10.1111/mmi.15108}},
volume = {{120}},
year = {{2023}},
}