---
APC_amount: 5949 EUR
OA_place: publisher
OA_type: hybrid
_id: '19626'
abstract:
- lang: eng
text: Active regulation of gene expression, orchestrated by complex interactions
of activators and repressors at promoters, controls the fate of organisms. In
contrast, basal expression at uninduced promoters is considered to be a dynamically
inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional
regulation. Here, we investigate the basal expression mode of the mar operon,
the main regulator of intrinsic multiple antibiotic resistance in Escherichia
coli, and link its dynamic properties to the noncanonical, yet highly conserved
start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements
across tens of generations reveal that basal expression consists of rare stochastic
gene expression pulses, which maximize variability in wildtype and, surprisingly,
transiently accelerate cellular elongation rates. Competition experiments show
that basal expression confers fitness advantages to wildtype across several transitions
between exponential and stationary growth by shortening lag times. The dynamically
rich basal expression of the mar operon has likely been evolutionarily maintained
for its role in growth homeostasis of Enterobacteria within the gut environment,
thereby allowing other ancillary gene regulatory roles to evolve, e.g., control
of costly-to-induce multidrug efflux pumps. Understanding the complex selection
forces governing genetic systems involved in intrinsic multidrug resistance is
crucial for effective public health measures.
acknowledged_ssus:
- _id: Bio
acknowledgement: K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions
on the manuscript, all other members from the Guet laboratory for valuable feedback,
R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria
for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic
Technology India for allowing time off to address the revisions. K.J. acknowledges
Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported
in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi),
O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant
ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.
article_number: e2413709122
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Kirti
full_name: Jain, Kirti
id: 330F0278-F248-11E8-B48F-1D18A9856A87
last_name: Jain
orcid: 0000-0002-3809-0449
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Olga
full_name: Bochkareva, Olga
id: C4558D3C-6102-11E9-A62E-F418E6697425
last_name: Bochkareva
orcid: 0000-0003-1006-6639
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile
basal gene expression as a fitness determinant in bacteria. Proceedings of
the National Academy of Sciences. 2025;122(15). doi:10.1073/pnas.2413709122
apa: Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., & Guet,
C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria.
Proceedings of the National Academy of Sciences. National Academy of Sciences.
https://doi.org/10.1073/pnas.2413709122
chicago: Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper
Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant
in Bacteria.” Proceedings of the National Academy of Sciences. National
Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2413709122.
ieee: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet,
“Pulsatile basal gene expression as a fitness determinant in bacteria,” Proceedings
of the National Academy of Sciences, vol. 122, no. 15. National Academy of
Sciences, 2025.
ista: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile
basal gene expression as a fitness determinant in bacteria. Proceedings of the
National Academy of Sciences. 122(15), e2413709122.
mla: Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant
in Bacteria.” Proceedings of the National Academy of Sciences, vol. 122,
no. 15, e2413709122, National Academy of Sciences, 2025, doi:10.1073/pnas.2413709122.
short: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings
of the National Academy of Sciences 122 (2025).
corr_author: '1'
date_created: 2025-04-27T22:02:13Z
date_published: 2025-04-15T00:00:00Z
date_updated: 2026-05-20T08:33:08Z
day: '15'
ddc:
- '570'
department:
- _id: CaGu
- _id: Bio
- _id: FyKo
- _id: GaTk
doi: 10.1073/pnas.2413709122
external_id:
isi:
- '001471235200001'
pmid:
- '40193613'
file:
- access_level: open_access
checksum: 115a687f40009660eb4b38b4f6559d41
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creator: dernst
date_created: 2025-06-24T07:27:43Z
date_updated: 2025-06-24T07:27:43Z
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file_name: 2025_PNAS_Jain.pdf
file_size: 2949523
relation: main_file
success: 1
file_date_updated: 2025-06-24T07:27:43Z
has_accepted_license: '1'
intvolume: ' 122'
isi: 1
issue: '15'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473
grant_number: CZI01
name: Tools for automation and feedback microscopy
- _id: bd6f94d1-d553-11ed-ba76-ae9f07250f74
grant_number: E219
name: Non-canonical antibiotic interactions
- _id: 34e076d6-11ca-11ed-8bc3-aec76c41a181
grant_number: I05127
name: Evolutionary analysis of gene regulation
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/
record:
- id: '19294'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Pulsatile basal gene expression as a fitness determinant in bacteria
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 122
year: '2025'
...