---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '21928'
abstract:
- lang: eng
text: Antibiotic combination in time and space is a key strategy to combat antimicrobial
resistance. The success of such treatment designs requires their robust efficacy
across treatment conditions and a pathogen’s genomic diversity. This study found
that an initial treatment with a β-lactam antibiotic causes robust cellular sensitization
towards an aminoglycoside antibiotic across the high-risk human pathogen Pseudomonas
aeruginosa, including resistant strains. This phenomenon of cellular sensitization,
termed negative hysteresis, is modulated by the Cpx envelope stress response system
and linked to membrane stress during growth. The increase in efficacy is achieved
through a β-lactam induced elevated cellular uptake of the subsequently administered
aminoglycoside. Negative hysteresis and the Cpx system are linked in several cases
to the expression of synergistic drug interactions, thus enhancing efficacy of
antibiotic combinations. Overall, our study identifies the phenomenon of negative
hysteresis as a robustly inducible phenotype and thus a unique focus for optimizing
antimicrobial therapy.
acknowledgement: "We are very grateful to S. Hernando-Amado (Madrid, Spain), C. Pál
(Szeged, Hungary), and T. Bollenbach (Cologne, Germany) for critical comments and
advice on the manuscript. We further thank D. Rogers, J. Summers (Ploen, Germany)
for guidance in allelic exchange, P. Rainey (Ploen, Germany) for providing the plasmids
and strains, then J. Lorenzen, K. Flinder, N. Steinbach, S. Butze (all Schulenburg
lab), and L. Kirchhoff (Rupp lab) for supporting the experimental work, and also
the Rupp and Schulenburg groups for general feedback. We are grateful for financial
support from the German Research Foundation within the Research and Training Group
2501 (RTG 2501) on Translational Evolutionary Research (project 4.2 to H.S.), within
the Excellence cluster Precision Medicine in chronic Inflammation (PMI; funding
under Germany’s Excellence Strategy EXC 2167-390884018, to B.K., K.R., J.R., H.S.),
within the Clinician Scientist Program in Evolutionary Medicine (CSEM) – project
number 413490537 (to EEG), and as part of the individual grants SCHU 1415/12-2 (to
H.S.) and BR-2915/7-1 (to M.B.). We are grateful for financial support from the
Swedish Research Council, project number 2021-02091 (to D.I.A.). We are also grateful
for financial support from the Max-Planck Society (Fellowship to H.S.), the Leibniz
Association within the Leibniz Science-Campus Evolutionary Medicine of the Lung
(EvoLUNG, to H.S.), and the project SKILLED funded by the DAMP foundation (to J.R.,
H.S.). This work was also supported by the ZMB Young Scientist award and the FWF
grant 10.55776/ESP219 (to R.R.) and the TransEvo Innovation prize (to F.B.). The
funders had no role in study design, data collection and interpretation, or the
decision to submit the work for publication. Open Access funding enabled and organized
by Projekt DEAL.\r\n"
article_number: '4487'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
full_name: Buchholz, Florian
last_name: Buchholz
- first_name: Lina M.
full_name: Upterworth, Lina M.
last_name: Upterworth
- first_name: Leif
full_name: Tueffers, Leif
last_name: Tueffers
- first_name: Espen E.
full_name: Groth, Espen E.
last_name: Groth
- first_name: Kira
full_name: Haas, Kira
last_name: Haas
- first_name: Daniel
full_name: Schütz, Daniel
last_name: Schütz
- first_name: Abigail
full_name: Savietto Scholz, Abigail
last_name: Savietto Scholz
- first_name: Aditi
full_name: Batra, Aditi
last_name: Batra
- first_name: Surajit
full_name: Pal, Surajit
last_name: Pal
- first_name: Samarpita
full_name: Banerjee, Samarpita
last_name: Banerjee
- first_name: Badri N.
full_name: Dubey, Badri N.
last_name: Dubey
- first_name: Sören
full_name: Franzenburg, Sören
last_name: Franzenburg
- first_name: Barbara
full_name: Kalsdorf, Barbara
last_name: Kalsdorf
- first_name: Klaus F.
full_name: Rabe, Klaus F.
last_name: Rabe
- first_name: Dennis
full_name: Nurjadi, Dennis
last_name: Nurjadi
- first_name: Jan
full_name: Rupp, Jan
last_name: Rupp
- first_name: Dan I.
full_name: Andersson, Dan I.
last_name: Andersson
- first_name: Holger
full_name: Sondermann, Holger
last_name: Sondermann
- first_name: Marc
full_name: Bramkamp, Marc
last_name: Bramkamp
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Hinrich
full_name: Schulenburg, Hinrich
last_name: Schulenburg
citation:
ama: Buchholz F, Upterworth LM, Tueffers L, et al. Robust antibiotic sensitization
of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope.
Nature Communications. 2026;17. doi:10.1038/s41467-026-71178-5
apa: Buchholz, F., Upterworth, L. M., Tueffers, L., Groth, E. E., Haas, K., Schütz,
D., … Schulenburg, H. (2026). Robust antibiotic sensitization of pathogenic Pseudomonas
aeruginosa via negative hysteresis in the cell envelope. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-026-71178-5
chicago: Buchholz, Florian, Lina M. Upterworth, Leif Tueffers, Espen E. Groth, Kira
Haas, Daniel Schütz, Abigail Savietto Scholz, et al. “Robust Antibiotic Sensitization
of Pathogenic Pseudomonas Aeruginosa via Negative Hysteresis in the Cell Envelope.”
Nature Communications. Springer Nature, 2026. https://doi.org/10.1038/s41467-026-71178-5.
ieee: F. Buchholz et al., “Robust antibiotic sensitization of pathogenic
Pseudomonas aeruginosa via negative hysteresis in the cell envelope,” Nature
Communications, vol. 17. Springer Nature, 2026.
ista: Buchholz F, Upterworth LM, Tueffers L, Groth EE, Haas K, Schütz D, Savietto
Scholz A, Batra A, Pal S, Banerjee S, Dubey BN, Franzenburg S, Kalsdorf B, Rabe
KF, Nurjadi D, Rupp J, Andersson DI, Sondermann H, Bramkamp M, Römhild R, Schulenburg
H. 2026. Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa
via negative hysteresis in the cell envelope. Nature Communications. 17, 4487.
mla: Buchholz, Florian, et al. “Robust Antibiotic Sensitization of Pathogenic Pseudomonas
Aeruginosa via Negative Hysteresis in the Cell Envelope.” Nature Communications,
vol. 17, 4487, Springer Nature, 2026, doi:10.1038/s41467-026-71178-5.
short: F. Buchholz, L.M. Upterworth, L. Tueffers, E.E. Groth, K. Haas, D. Schütz,
A. Savietto Scholz, A. Batra, S. Pal, S. Banerjee, B.N. Dubey, S. Franzenburg,
B. Kalsdorf, K.F. Rabe, D. Nurjadi, J. Rupp, D.I. Andersson, H. Sondermann, M.
Bramkamp, R. Römhild, H. Schulenburg, Nature Communications 17 (2026).
corr_author: '1'
date_created: 2026-05-31T22:02:12Z
date_published: 2026-05-20T00:00:00Z
date_updated: 2026-06-02T07:14:35Z
day: '20'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1038/s41467-026-71178-5
file:
- access_level: open_access
checksum: aa29f8806908dc0469dff21e2d5ad01f
content_type: application/pdf
creator: dernst
date_created: 2026-06-02T07:11:12Z
date_updated: 2026-06-02T07:11:12Z
file_id: '21936'
file_name: 2026_NatureComm_Buchholz.pdf
file_size: 1276166
relation: main_file
success: 1
file_date_updated: 2026-06-02T07:11:12Z
has_accepted_license: '1'
intvolume: ' 17'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: bd6f94d1-d553-11ed-ba76-ae9f07250f74
grant_number: E219
name: Non-canonical antibiotic interactions
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative
hysteresis in the cell envelope
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: 17
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21983'
abstract:
- lang: eng
text: 'Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences
that bind transcription factor (TF) proteins to up- or down-regulate target genes.
Decades-long efforts yielded TF-DNA interaction models that predict how strongly
an individual TF binds arbitrary DNA sequences and how individual binding events
on the CRE combine to affect gene expression. These insights can be synthesized
into a global, biophysically realistic, and quantitative genotype–phenotype map
for gene regulation, a ‘holy grail’ for the application of evolutionary theory.
A global map provides a rare opportunity to simulate the long-term evolution of
regulatory sequences and pose several fundamental questions: How long does it
take to evolve CREs de novo? How many non-trivial regulatory functions exist in
sequence space? How connected are they? For which regulatory architecture is CRE
evolution most rapid and evolvable? In this article, the first of a two-part series,
we briefly review the pertinent modeling and simulation efforts for a unique system
that enables close, quantitative, and mechanistic links between biophysics, as
well as systems, synthetic, and evolutionary biology.'
acknowledgement: "We thank Nick Barton and Noa Ottilie Borst for essential contributions
to this manuscript.\r\nE.M. acknowledges support from the APART-USA fellowship,
jointly funded by the Austrian Academy of Sciences (ÖAW) and the Institute of Science
and Technology Austria (ISTA).\r\nThis study was supported by the European Molecular
Biology Laboratory (J.C.); the European Molecular Biology Laboratory Interdisciplinary
Postdoc Programme (EIPOD) under the Marie Skłodowska-Curie Actions cofund (S.H.A.)."
article_number: '102483'
article_processing_charge: Yes (via OA deal)
article_type: original
arxiv: 1
author:
- first_name: Elia
full_name: Mascolo, Elia
id: 776a6ed0-a053-11f0-8635-80b95e0e0d53
last_name: Mascolo
orcid: 0000-0003-2977-7844
- first_name: Reka E
full_name: Körei, Reka E
id: 50FDE43E-AA30-11E9-A72B-8A12E6697425
last_name: Körei
- first_name: Santiago
full_name: Herrera-Álvarez, Santiago
last_name: Herrera-Álvarez
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Justin
full_name: Crocker, Justin
last_name: Crocker
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: 'Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. Long-term
evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic
genotype–phenotype maps. Current Opinion in Genetics & Development.
2026;99. doi:10.1016/j.gde.2026.102483'
apa: 'Mascolo, E., Körei, R. E., Herrera-Álvarez, S., Guet, C. C., Crocker, J.,
& Tkačik, G. (2026). Long-term evolution of regulatory DNA sequences. Part
1: Simulations on global, biophysically-realistic genotype–phenotype maps. Current
Opinion in Genetics & Development. Elsevier. https://doi.org/10.1016/j.gde.2026.102483'
chicago: 'Mascolo, Elia, Reka E Körei, Santiago Herrera-Álvarez, Calin C Guet, Justin
Crocker, and Gašper Tkačik. “Long-Term Evolution of Regulatory DNA Sequences.
Part 1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.”
Current Opinion in Genetics & Development. Elsevier, 2026. https://doi.org/10.1016/j.gde.2026.102483.'
ieee: 'E. Mascolo, R. E. Körei, S. Herrera-Álvarez, C. C. Guet, J. Crocker, and
G. Tkačik, “Long-term evolution of regulatory DNA sequences. Part 1: Simulations
on global, biophysically-realistic genotype–phenotype maps,” Current Opinion
in Genetics & Development, vol. 99. Elsevier, 2026.'
ista: 'Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. 2026.
Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global,
biophysically-realistic genotype–phenotype maps. Current Opinion in Genetics &
Development. 99, 102483.'
mla: 'Mascolo, Elia, et al. “Long-Term Evolution of Regulatory DNA Sequences. Part
1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.” Current
Opinion in Genetics & Development, vol. 99, 102483, Elsevier, 2026, doi:10.1016/j.gde.2026.102483.'
short: E. Mascolo, R.E. Körei, S. Herrera-Álvarez, C.C. Guet, J. Crocker, G. Tkačik,
Current Opinion in Genetics & Development 99 (2026).
corr_author: '1'
date_created: 2026-06-10T07:37:12Z
date_published: 2026-05-09T00:00:00Z
date_updated: 2026-06-16T12:37:02Z
day: '09'
ddc:
- '570'
department:
- _id: GradSch
- _id: CaGu
- _id: GaTk
doi: 10.1016/j.gde.2026.102483
external_id:
arxiv:
- '2601.19681'
has_accepted_license: '1'
intvolume: ' 99'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.gde.2026.102483
month: '05'
oa: 1
oa_version: Published Version
publication: Current Opinion in Genetics & Development
publication_identifier:
eissn:
- 1879-0380
issn:
- 0959-437X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global,
biophysically-realistic genotype–phenotype maps'
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: 99
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21985'
abstract:
- lang: eng
text: Upon infecting a bacterial cell, temperate phages make a decision between
lysis and lysogeny. While research has previously explored how phages sense environmental
information to make this choice, most studies have focused on modelling known
mechanisms that impact the decision. These mechanisms tell us what environmental
information the phage does respond to, but not what it should respond to, as the
signals sensed by the phage may serve as proxies for other sources of information.
Here, using a mechanism-agnostic population dynamics model, we find that irreversible
phage binding to lysogens protects sensitive host cells from infection. This results
in lysogens being an additional environmental factor that the phage should sense
while making its decision to undergo lysis or lysogeny. Using this model, we derive
a responsive lysogeny probability for phages that respond to both cell and lysogen
densities optimized towards invading phage-occupied systems, and show that it
is more capable of invading and resisting invasion than phage with fixed lysogeny
probabilities across different environmental conditions.
acknowledgement: We thank Fyodor Kondrashov and Gašper Tkačik for valuable input and
guidance in building the model, and Stephen Abedon as well as the two anonymous
reviewers for the comments provided on the manuscript.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Bryan
full_name: Wu, Bryan
id: 3C521EBA-F248-11E8-B48F-1D18A9856A87
last_name: Wu
- 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: Wu B, Guet CC. Responsive lysogeny under nonproductive phage binding. Evolution.
2026;80(6):1365-1373. doi:10.1093/evolut/qpag061
apa: Wu, B., & Guet, C. C. (2026). Responsive lysogeny under nonproductive phage
binding. Evolution. Oxford University Press. https://doi.org/10.1093/evolut/qpag061
chicago: Wu, Bryan, and Calin C Guet. “Responsive Lysogeny under Nonproductive Phage
Binding.” Evolution. Oxford University Press, 2026. https://doi.org/10.1093/evolut/qpag061.
ieee: B. Wu and C. C. Guet, “Responsive lysogeny under nonproductive phage binding,”
Evolution, vol. 80, no. 6. Oxford University Press, pp. 1365–1373, 2026.
ista: Wu B, Guet CC. 2026. Responsive lysogeny under nonproductive phage binding.
Evolution. 80(6), 1365–1373.
mla: Wu, Bryan, and Calin C. Guet. “Responsive Lysogeny under Nonproductive Phage
Binding.” Evolution, vol. 80, no. 6, Oxford University Press, 2026, pp.
1365–73, doi:10.1093/evolut/qpag061.
short: B. Wu, C.C. Guet, Evolution 80 (2026) 1365–1373.
corr_author: '1'
date_created: 2026-06-10T07:38:12Z
date_published: 2026-06-01T00:00:00Z
date_updated: 2026-06-16T12:46:02Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1093/evolut/qpag061
external_id:
pmid:
- '41968110'
file:
- access_level: open_access
checksum: 6d0f48566a7a36cb0c469e1968c9cb1c
content_type: application/pdf
creator: dernst
date_created: 2026-06-16T12:45:09Z
date_updated: 2026-06-16T12:45:09Z
file_id: '22015'
file_name: 2026_Evolution_Wu.pdf
file_size: 2077781
relation: main_file
success: 1
file_date_updated: 2026-06-16T12:45:09Z
has_accepted_license: '1'
intvolume: ' 80'
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 1365-1373
pmid: 1
publication: Evolution
publication_identifier:
eissn:
- 1558-5646
issn:
- 0014-3820
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/theguetlab/responsive-lysogeny
scopus_import: '1'
status: public
title: Responsive lysogeny under nonproductive phage binding
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: 80
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
_id: '19857'
abstract:
- lang: eng
text: Bacteria have evolved a wide range of defence strategies to protect themselves
against bacterial viruses (phages). Most known bacterial antiphage defence systems
target phages with DNA genomes, which raises the question of how bacteria defend
against phages with RNA genomes. Bacterial toxin–antitoxin systems that cleave
intracellular RNA could potentially protect bacteria against RNA phages, but this
has not been explored experimentally. In this study, we investigated the role
of a model toxin–antitoxin system, MazEF, in protecting Escherichia coli against
two RNA phage species. When challenged with these phages, the native presence
of mazEF moderately reduced population susceptibility and increased the survival
of individual E. coli cells. Genomic analysis further revealed an underrepresentation
of the MazF cleavage site in genomes of RNA phages infecting E. coli, indicating
selection against cleavage. These results show that, in addition to other physiological
roles, RNA-degrading toxin–antitoxin systems may also help defend against RNA
phages.
acknowledged_ssus:
- _id: LifeSc
acknowledgement: This work was supported by ISTFELLOW (People Program – Marie Curie
Actions of the European Union’s Seventh Framework Program FP7 under REA grant agreement
291734), the FWF (Austrian Science Fund) Elise Richter Program project number V
738 and the Wellcome Trust Institutional Strategic Support Award (WT105618MA), to
N.N. M.P. was a Simons Foundation Fellow of the Life Sciences Research Foundation.
We are grateful to Kathrin Tomasek, Lisa Butt, Chris Estell, Alys Jepson, Franklin
Nobrega, Stefano Pagliara, Remy Chait, Steve West, Vicki Gold, Josh Eaton, Ivana
Gudelj and Rob Beardmore for useful discussions and technical support, as well as
to Robin Wright, Christian Fitch and Ben Temperton for sharing equipment. We thank
Laurence Van Melderen for sharing the strains. We acknowledge the IST Austria Lab
Support Facility, LSI Technical Services Team at the University of Exeter and the
Translational Research Exchange @ Exeter (TREE) network. N.N. is grateful to Fabrice
Gielen for his support.
article_number: '20250080'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- 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: Nikolic N, Pleska M, Bergmiller T, Guet CC. A bacterial toxin-antitoxin system
as a native defence element against RNA phages. Biology Letters. 2025;21(6).
doi:10.1098/rsbl.2025.0080
apa: Nikolic, N., Pleska, M., Bergmiller, T., & Guet, C. C. (2025). A bacterial
toxin-antitoxin system as a native defence element against RNA phages. Biology
Letters. The Royal Society. https://doi.org/10.1098/rsbl.2025.0080
chicago: Nikolic, Nela, Maros Pleska, Tobias Bergmiller, and Calin C Guet. “A Bacterial
Toxin-Antitoxin System as a Native Defence Element against RNA Phages.” Biology
Letters. The Royal Society, 2025. https://doi.org/10.1098/rsbl.2025.0080.
ieee: N. Nikolic, M. Pleska, T. Bergmiller, and C. C. Guet, “A bacterial toxin-antitoxin
system as a native defence element against RNA phages,” Biology Letters,
vol. 21, no. 6. The Royal Society, 2025.
ista: Nikolic N, Pleska M, Bergmiller T, Guet CC. 2025. A bacterial toxin-antitoxin
system as a native defence element against RNA phages. Biology Letters. 21(6),
20250080.
mla: Nikolic, Nela, et al. “A Bacterial Toxin-Antitoxin System as a Native Defence
Element against RNA Phages.” Biology Letters, vol. 21, no. 6, 20250080,
The Royal Society, 2025, doi:10.1098/rsbl.2025.0080.
short: N. Nikolic, M. Pleska, T. Bergmiller, C.C. Guet, Biology Letters 21 (2025).
corr_author: '1'
date_created: 2025-06-22T22:02:06Z
date_published: 2025-06-11T00:00:00Z
date_updated: 2025-09-30T13:38:08Z
day: '11'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1098/rsbl.2025.0080
ec_funded: 1
external_id:
isi:
- '001505019800001'
pmid:
- '40494395'
file:
- access_level: open_access
checksum: 016f644ed068f8609ded306ad26dbd3f
content_type: application/pdf
creator: dernst
date_created: 2025-06-23T11:34:39Z
date_updated: 2025-06-23T11:34:39Z
file_id: '19873'
file_name: 2025_BiologyLetters_Nikolic.pdf
file_size: 1850797
relation: main_file
success: 1
file_date_updated: 2025-06-23T11:34:39Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 26956E74-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00738
name: Bacterial toxin-antitoxin systems as antiphage defense mechanisms
publication: Biology Letters
publication_identifier:
eissn:
- 1744-957X
issn:
- 1744-9561
publication_status: published
publisher: The Royal Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: A bacterial toxin-antitoxin system as a native defence element against RNA
phages
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 21
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18936'
abstract:
- lang: eng
text: A major obstacle to predictive understanding of evolution stems from the complexity
of biological systems, which prevents detailed characterization of key evolutionary
properties. Here, we highlight some of the major sources of complexity that arise
when relating molecular mechanisms to their evolutionary consequences and ask
whether accounting for every mechanistic detail is important to accurately predict
evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial
promoter regulated by 2 proteins, allowing us to connect any promoter genotype
to 6 phenotypes that capture the dynamics of gene expression following an environmental
switch. Accounting for the mechanisms that govern how this system works enabled
us to provide an in-depth picture of how regulated bacterial promoters might evolve.
More importantly, we used the model to explore which factors that contribute to
the complexity of this system are essential for understanding its evolution, and
which can be simplified without information loss. We found that several key evolutionary
properties—the distribution of phenotypic and fitness effects of mutations, the
evolutionary trajectories during selection for regulation—can be accurately captured
without accounting for all, or even most, parameters of the system. Our findings
point to the need for a mechanistic approach to studying evolution, as it enables
tackling biological complexity and in doing so improves the ability to predict
evolutionary outcomes.
acknowledgement: "The authors thank Nick Barton, Stepan Denisov, Claudia Igler, Srdjan
Sarikas, Anna Staron, and the anonymous reviewers for useful comments and discussions
that helped improve our work.\r\nFunding for this work was provided by the Wellcome
Trust–Royal Society Sir Henry Dale Fellowship (216779/Z/19/Z) and the Royal Society
Research Grant (RG\\R2\\232522) to M.L."
article_number: iyae191
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
citation:
ama: 'Grah R, Guet CC, Tkačik G, Lagator M. Linking molecular mechanisms to their
evolutionary consequences: a primer. Genetics. 2025;229(2). doi:10.1093/genetics/iyae191'
apa: 'Grah, R., Guet, C. C., Tkačik, G., & Lagator, M. (2025). Linking molecular
mechanisms to their evolutionary consequences: a primer. Genetics. Oxford
University Press. https://doi.org/10.1093/genetics/iyae191'
chicago: 'Grah, Rok, Calin C Guet, Gašper Tkačik, and Mato Lagator. “Linking Molecular
Mechanisms to Their Evolutionary Consequences: A Primer.” Genetics. Oxford
University Press, 2025. https://doi.org/10.1093/genetics/iyae191.'
ieee: 'R. Grah, C. C. Guet, G. Tkačik, and M. Lagator, “Linking molecular mechanisms
to their evolutionary consequences: a primer,” Genetics, vol. 229, no.
2. Oxford University Press, 2025.'
ista: 'Grah R, Guet CC, Tkačik G, Lagator M. 2025. Linking molecular mechanisms
to their evolutionary consequences: a primer. Genetics. 229(2), iyae191.'
mla: 'Grah, Rok, et al. “Linking Molecular Mechanisms to Their Evolutionary Consequences:
A Primer.” Genetics, vol. 229, no. 2, iyae191, Oxford University Press,
2025, doi:10.1093/genetics/iyae191.'
short: R. Grah, C.C. Guet, G. Tkačik, M. Lagator, Genetics 229 (2025).
corr_author: '1'
date_created: 2025-01-29T08:21:35Z
date_published: 2025-02-01T00:00:00Z
date_updated: 2025-05-19T14:08:02Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1093/genetics/iyae191
external_id:
isi:
- '001379194200001'
pmid:
- '39601269'
file:
- access_level: open_access
checksum: f730e416795969449ef49d97b82ac494
content_type: application/pdf
creator: dernst
date_created: 2025-04-16T09:41:04Z
date_updated: 2025-04-16T09:41:04Z
file_id: '19580'
file_name: 2025_Genetics_Grah.pdf
file_size: 1511688
relation: main_file
success: 1
file_date_updated: 2025-04-16T09:41:04Z
has_accepted_license: '1'
intvolume: ' 229'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Genetics
publication_identifier:
eissn:
- 1943-2631
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Linking molecular mechanisms to their evolutionary consequences: a primer'
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: 229
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19725'
abstract:
- lang: eng
text: Protein-protein interactions (PPIs) mediate many fundamental cellular processes.
Control of PPIs through optically or chemically responsive protein domains has
had a profound impact on basic research and some clinical applications. Most chemogenetic
methods induce the association, i.e., dimerization or oligomerization, of target
proteins, whilst the few available dissociation approaches either break large
oligomeric protein clusters or heteromeric complexes. Here, we have exploited
the controlled dissociation of a homodimeric oxidoreductase from mycobacteria
(MSMEG_2027) by its native cofactor, F420, which is not present in mammals, as
a bioorthogonal monomerization switch. Using X-ray crystallography, we found that
in the absence of F420 MSMEG_2027 forms a unique domain-swapped dimer that occludes
the cofactor binding site. Rearrangement of the N-terminal helix upon F420 binding
results in the dissolution of the dimer. We then showed that MSMEG_2027 can be
fused to proteins of interest in human cells and applied it as a tool to induce
and release MAPK/ERK signalling downstream of a chimeric fibroblast growth factor
receptor 1 (FGFR1) tyrosine kinase. This F420-dependent chemogenetic de-homodimerization
tool is stoichiometric and based on a single domain and thus represents a novel
mechanism to investigate protein complexes in situ.
acknowledgement: We thank J. Kaczmarski for advice on isothermal titration calorimetry
and helpful comments, and Alexandra Tichy, Elliot Gerrard and Rahkesh T Sabapathy
for assistance with experiments. This study was supported by grants of the Australian
Research Council (FT200100519 and DP200102093, to H.J.; DE190100806, DP220101901,
FT230100203, and DP250102939 to T.P.S.D.C; DP200102093, CE200100029 and CE200100012
to C.J.J.), the National Health and Medical Research Council (APP1187638, to H.J.).
S.K. was supported by the graduate program MolecularDrugTargets (Austrian Science
Fund FWF W1232). The Australian Regenerative Medicine Institute is supported by
grants from the State Government of Victoria and the Australian Government. The
EMBL Australia Partnership Laboratory (EMBL Australia) is supported by the National
Collaborative Research Infrastructure Strategy (NCRIS) of the Australian Government.
T.P.S.D.C. acknowledges the University of Adelaide for a Future Making Fellowship.
E.R.R.M acknowledges the Grains Research and Development Corporation (9176977) for
support through a PhD scholarship and operational funding. J.A. and E.R.R.M. were
supported by Australian Research Training Program scholarship. MicroMon of Monash
University provided Sanger sequencing services. Imaging was performed in the CellScreen
SA screening center of Flinders University. C.J.J. thanks the ARC Centre of Excellence
for Innovations in Peptide and Protein Science and the ARC Centre of Excellence
in Synthetic Biology. We thank the staff of the MX2 beamline at the Australian Synchrotron,
part of ANSTO, which made use of the Australian Cancer Research Foundation (ACRF)
detector.
article_number: '169184'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: James
full_name: Antoney, James
last_name: Antoney
- first_name: Stephanie
full_name: Kainrath, Stephanie
id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
last_name: Kainrath
orcid: 0000-0002-6709-2195
- first_name: Joshua G.
full_name: Dubowsky, Joshua G.
last_name: Dubowsky
- first_name: F. Hafna
full_name: Ahmed, F. Hafna
last_name: Ahmed
- first_name: Suk Woo
full_name: Kang, Suk Woo
last_name: Kang
- first_name: Emily R.R.
full_name: Mackie, Emily R.R.
last_name: Mackie
- first_name: Gustavo
full_name: Bracho Granado, Gustavo
last_name: Bracho Granado
- first_name: Tatiana P.
full_name: Soares Da Costa, Tatiana P.
last_name: Soares Da Costa
- first_name: Colin J.
full_name: Jackson, Colin J.
last_name: Jackson
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
citation:
ama: Antoney J, Kainrath S, Dubowsky JG, et al. A F420-dependent single domain chemogenetic
tool for protein de-dimerization. Journal of Molecular Biology. 2025;437(17).
doi:10.1016/j.jmb.2025.169184
apa: Antoney, J., Kainrath, S., Dubowsky, J. G., Ahmed, F. H., Kang, S. W., Mackie,
E. R. R., … Janovjak, H. L. (2025). A F420-dependent single domain chemogenetic
tool for protein de-dimerization. Journal of Molecular Biology. Elsevier.
https://doi.org/10.1016/j.jmb.2025.169184
chicago: Antoney, James, Stephanie Kainrath, Joshua G. Dubowsky, F. Hafna Ahmed,
Suk Woo Kang, Emily R.R. Mackie, Gustavo Bracho Granado, Tatiana P. Soares Da
Costa, Colin J. Jackson, and Harald L Janovjak. “A F420-Dependent Single Domain
Chemogenetic Tool for Protein de-Dimerization.” Journal of Molecular Biology.
Elsevier, 2025. https://doi.org/10.1016/j.jmb.2025.169184.
ieee: J. Antoney et al., “A F420-dependent single domain chemogenetic tool
for protein de-dimerization,” Journal of Molecular Biology, vol. 437, no.
17. Elsevier, 2025.
ista: Antoney J, Kainrath S, Dubowsky JG, Ahmed FH, Kang SW, Mackie ERR, Bracho
Granado G, Soares Da Costa TP, Jackson CJ, Janovjak HL. 2025. A F420-dependent
single domain chemogenetic tool for protein de-dimerization. Journal of Molecular
Biology. 437(17), 169184.
mla: Antoney, James, et al. “A F420-Dependent Single Domain Chemogenetic Tool for
Protein de-Dimerization.” Journal of Molecular Biology, vol. 437, no. 17,
169184, Elsevier, 2025, doi:10.1016/j.jmb.2025.169184.
short: J. Antoney, S. Kainrath, J.G. Dubowsky, F.H. Ahmed, S.W. Kang, E.R.R. Mackie,
G. Bracho Granado, T.P. Soares Da Costa, C.J. Jackson, H.L. Janovjak, Journal
of Molecular Biology 437 (2025).
date_created: 2025-05-25T22:16:39Z
date_published: 2025-09-01T00:00:00Z
date_updated: 2025-12-30T08:18:25Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1016/j.jmb.2025.169184
external_id:
isi:
- '001494762800001'
pmid:
- '40324743'
file:
- access_level: open_access
checksum: fb6e84ba7dc92faee97647fd2bc8cca8
content_type: application/pdf
creator: dernst
date_created: 2025-12-30T08:18:07Z
date_updated: 2025-12-30T08:18:07Z
file_id: '20892'
file_name: 2025_JourMolecularBiology_Antoney.pdf
file_size: 1682721
relation: main_file
success: 1
file_date_updated: 2025-12-30T08:18:07Z
has_accepted_license: '1'
intvolume: ' 437'
isi: 1
issue: '17'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 255A6082-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Journal of Molecular Biology
publication_identifier:
eissn:
- 1089-8638
issn:
- 0022-2836
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A F420-dependent single domain chemogenetic tool for protein de-dimerization
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: 437
year: '2025'
...
---
APC_amount: 3642,79 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20080'
abstract:
- lang: eng
text: "Introduction: Acid-growth theory has been postulated in the 70s to explain
the rapid elongation of plant cells in response to the hormone auxin. More recently,
it has been demonstrated that activation of the proton ATPs pump (H+-ATPs) promoting
acidification of the apoplast is the principal mechanism by which auxin and other
hormones such as brassinosteroids (BR) induce cell elongation. Despite these advances,
the impact of this acidification on the mechanical properties of the cell wall
remained largely unexplored.\r\n\r\nMethods: Here, we use elongation assays of
Arabidopsis thaliana hypocotyls and Atomic Force Microscopy (AFM) to correlate
hormone-induced tissue elongation and local changes in cell wall mechanical properties.
Furthermore, employing transgenic lines over-expressing Pectin Methyl Esterase
(PME), along with calcium chelators, we investigate the effect of pectin modification
in hormone-driven cell elongation.\r\n\r\nResults: We demonstrate that acidification
of apoplast is necessary and sufficient to induce cell elongation through promoting
cell wall softening. Moreover, we show that enhanced PME activity can induce both
cell wall softening or stiffening in extracellular calcium dependent-manner and
that tight control of PME activity is required for proper hypocotyl elongation.\r\n\r\nDiscussion:
Our results confirm a dual role of PME in plant cell elongation. However, further
investigation is needed to assess the status of pectin following short- or long-term
PME treatments in order to determine if pectin methyl-esterification might promote
its degradation as well as the role of PME inhibitors upon PME induction."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: E-Lib
acknowledgement: "The author(s) declare that financial support was received for the
research and/or publication of this article. This work was supported by grants from
the European Research Council (Starting Independent Research Grant ERC-2007-Stg-
207362-HCPO to EB) and MG was recipient of an IST Interdisciplinary project (IC1022IPC03).\r\nWe
acknowledge Jaume F. Martı́nez Garcı́a for phyAphyB mutant seeds. We acknowledge
CF Nanobiotechnology of CIISB, Instruct-CZ Centre, supported by MEYS CR (LM2018127).
We gratefully acknowledge support by the Scientific Service Units at ISTA, including
the Imaging and Optics and Lab Support facilities and Library. We thank Stefan Riegler
for the efforts to establish immunodetection method."
article_number: '1612366'
article_processing_charge: Yes
article_type: original
author:
- first_name: Marçal
full_name: Gallemi, Marçal
id: 460C6802-F248-11E8-B48F-1D18A9856A87
last_name: Gallemi
orcid: 0000-0003-4675-6893
- first_name: Juan C
full_name: Montesinos López, Juan C
id: 310A8E3E-F248-11E8-B48F-1D18A9856A87
last_name: Montesinos López
orcid: 0000-0001-9179-6099
- first_name: Nikola
full_name: Zarevski, Nikola
id: 18e95355-e05a-11ea-a9c0-8fba1b89e83a
last_name: Zarevski
- first_name: Jan
full_name: Pribyl, Jan
last_name: Pribyl
- first_name: Petr
full_name: Skládal, Petr
last_name: Skládal
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Eva
full_name: Benková, Eva
id: 38F4F166-F248-11E8-B48F-1D18A9856A87
last_name: Benková
orcid: 0000-0002-8510-9739
citation:
ama: Gallemi M, Montesinos López JC, Zarevski N, et al. Dual role of pectin methyl
esterase activity in the regulation of plant cell wall biophysical properties.
Frontiers in Plant Science. 2025;16. doi:10.3389/fpls.2025.1612366
apa: Gallemi, M., Montesinos López, J. C., Zarevski, N., Pribyl, J., Skládal, P.,
Hannezo, E. B., & Benková, E. (2025). Dual role of pectin methyl esterase
activity in the regulation of plant cell wall biophysical properties. Frontiers
in Plant Science. Frontiers Media. https://doi.org/10.3389/fpls.2025.1612366
chicago: Gallemi, Marçal, Juan C Montesinos López, Nikola Zarevski, Jan Pribyl,
Petr Skládal, Edouard B Hannezo, and Eva Benková. “Dual Role of Pectin Methyl
Esterase Activity in the Regulation of Plant Cell Wall Biophysical Properties.”
Frontiers in Plant Science. Frontiers Media, 2025. https://doi.org/10.3389/fpls.2025.1612366.
ieee: M. Gallemi et al., “Dual role of pectin methyl esterase activity in
the regulation of plant cell wall biophysical properties,” Frontiers in Plant
Science, vol. 16. Frontiers Media, 2025.
ista: Gallemi M, Montesinos López JC, Zarevski N, Pribyl J, Skládal P, Hannezo EB,
Benková E. 2025. Dual role of pectin methyl esterase activity in the regulation
of plant cell wall biophysical properties. Frontiers in Plant Science. 16, 1612366.
mla: Gallemi, Marçal, et al. “Dual Role of Pectin Methyl Esterase Activity in the
Regulation of Plant Cell Wall Biophysical Properties.” Frontiers in Plant Science,
vol. 16, 1612366, Frontiers Media, 2025, doi:10.3389/fpls.2025.1612366.
short: M. Gallemi, J.C. Montesinos López, N. Zarevski, J. Pribyl, P. Skládal, E.B.
Hannezo, E. Benková, Frontiers in Plant Science 16 (2025).
corr_author: '1'
date_created: 2025-07-27T22:01:26Z
date_published: 2025-07-04T00:00:00Z
date_updated: 2026-05-20T07:53:03Z
day: '04'
ddc:
- '580'
department:
- _id: EdHa
- _id: EvBe
- _id: CaGu
doi: 10.3389/fpls.2025.1612366
ec_funded: 1
external_id:
isi:
- '001530690900001'
pmid:
- '40688689'
file:
- access_level: open_access
checksum: 9e6b8b53ba56d4a24a9bd91cf6d2dc58
content_type: application/pdf
creator: dernst
date_created: 2025-07-31T07:28:54Z
date_updated: 2025-07-31T07:28:54Z
file_id: '20093'
file_name: 2025_FrontiersPlantSc_Gallemi.pdf
file_size: 3665187
relation: main_file
success: 1
file_date_updated: 2025-07-31T07:28:54Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 253FCA6A-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '207362'
name: Hormonal cross-talk in plant organogenesis
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
publication: Frontiers in Plant Science
publication_identifier:
eissn:
- 1664-462X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dual role of pectin methyl esterase activity in the regulation of plant cell
wall biophysical properties
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: 16
year: '2025'
...
---
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
content_type: application/pdf
creator: dernst
date_created: 2025-06-24T07:27:43Z
date_updated: 2025-06-24T07:27:43Z
file_id: '19888'
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
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'
...
---
OA_place: repository
OA_type: gold
_id: '19294'
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 non-functional “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 non-canonical, 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 multi-drug efflux pumps. Understanding the complex selection
forces governing genetic systems involved in intrinsic multi-drug resistance is
crucial for effective public health measures.
article_processing_charge: No
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. Data for “Pulsatile
basal gene expression as a fitness determinant in bacteria.” 2025. doi:10.15479/AT:ISTA:19294
apa: Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., & Guet,
C. C. (2025). Data for “Pulsatile basal gene expression as a fitness determinant
in bacteria.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:19294
chicago: Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper
Tkačik, and Calin C Guet. “Data for ‘Pulsatile Basal Gene Expression as a Fitness
Determinant in Bacteria.’” Institute of Science and Technology Austria, 2025.
https://doi.org/10.15479/AT:ISTA:19294.
ieee: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet,
“Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria.’”
Institute of Science and Technology Austria, 2025.
ista: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Data
for ‘Pulsatile basal gene expression as a fitness determinant in bacteria’, Institute
of Science and Technology Austria, 10.15479/AT:ISTA:19294.
mla: Jain, Kirti, et al. Data for “Pulsatile Basal Gene Expression as a Fitness
Determinant in Bacteria.” Institute of Science and Technology Austria, 2025,
doi:10.15479/AT:ISTA:19294.
short: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, (2025).
corr_author: '1'
date_created: 2025-03-04T13:27:21Z
date_published: 2025-03-04T00:00:00Z
date_updated: 2026-05-20T08:33:07Z
day: '04'
ddc:
- '570'
department:
- _id: CaGu
- _id: Bio
- _id: FyKo
- _id: GaTk
doi: 10.15479/AT:ISTA:19294
file:
- access_level: open_access
checksum: 11a5bab307a4e1e1598a1577d8a2fbb5
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: dernst
date_created: 2025-03-04T13:08:52Z
date_updated: 2025-03-04T13:08:52Z
file_id: '19295'
file_name: Data1.xlsx
file_size: 269054
relation: main_file
success: 1
- access_level: open_access
checksum: 3b057894322639f0c1e11fb2e84173e6
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: dernst
date_created: 2025-03-04T13:08:52Z
date_updated: 2025-03-04T13:08:52Z
file_id: '19296'
file_name: Data2.xlsx
file_size: 87143
relation: main_file
success: 1
- access_level: open_access
checksum: a551e1b79a138bb97ab96979aa475b3c
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: dernst
date_created: 2025-03-04T13:08:52Z
date_updated: 2025-03-04T13:08:52Z
file_id: '19297'
file_name: Data3.xlsx
file_size: 129101
relation: main_file
success: 1
- access_level: open_access
checksum: d6909c9bf111f859058082b1a2f970c4
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: dernst
date_created: 2025-03-04T13:08:52Z
date_updated: 2025-03-04T13:08:52Z
file_id: '19298'
file_name: Data4.xlsx
file_size: 86243
relation: main_file
success: 1
- access_level: open_access
checksum: e5725a3a118a3f06846104906c8792c7
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: dernst
date_created: 2025-03-04T13:08:52Z
date_updated: 2025-03-04T13:08:52Z
file_id: '19299'
file_name: Data5.xlsx
file_size: 26049
relation: main_file
success: 1
- access_level: open_access
checksum: 16763c127049f14bd587dc885677dce1
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: dernst
date_created: 2025-03-04T13:08:52Z
date_updated: 2025-03-04T13:08:52Z
file_id: '19300'
file_name: RawData_2_3.xlsx
file_size: 7327253
relation: main_file
success: 1
- access_level: open_access
checksum: 2f3e1a368b4e3abc46bf37e02724f0f4
content_type: text/plain
creator: dernst
date_created: 2025-03-05T07:39:38Z
date_updated: 2025-03-05T07:39:38Z
file_id: '19301'
file_name: Readme.txt
file_size: 606
relation: main_file
success: 1
file_date_updated: 2025-03-05T07:39:38Z
has_accepted_license: '1'
month: '03'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '19626'
relation: used_in_publication
status: public
status: public
title: Data for "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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
_id: '20470'
abstract:
- lang: eng
text: "Systems design has classically relied on composable systems, in which individual
subsystems\r\nhave defined inputs, outputs, and interactions with each other;
however, attempts at\r\ndesigning complex systems in synthetic biology has often
run in to issues of crosstalk and\r\ninterference, given that these systems must
function within the context of the host. In nature,\r\nmobile genetic elements
are systems that have evolved to travel between hosts, and thus\r\nappear to be
a good candidate with which to evaluate composability. Selecting temperate\r\nphages
as a model system, I used mathematical modelling to identify sources of information\r\nthat
temperate phages should respond to. I found that essential proteins of temperate
phages\r\ncan interfere with potential hosts, indicating limitations to composability.
I also designed a\r\nlysogeny reporter construct and characterize its behavior
across various laboratory and\r\nenvironmental strains, finding differences in
phage lambda lysogens, and potential\r\ninterference from prophages that already
exist within the environmental strains. Although\r\nthe information gathered is
not conclusive, it suggests that composability is not a key property\r\nof temperate
phages, implying that biological systems may not be composable, and that other\r\nsystem
design principles should be considered when designing synthetic systems."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Bryan
full_name: Wu, Bryan
id: 3C521EBA-F248-11E8-B48F-1D18A9856A87
last_name: Wu
citation:
ama: Wu B. An examination on phages as a naturally composable system. 2025. doi:10.15479/AT-ISTA-20470
apa: Wu, B. (2025). An examination on phages as a naturally composable system.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20470
chicago: Wu, Bryan. “An Examination on Phages as a Naturally Composable System.”
Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20470.
ieee: B. Wu, “An examination on phages as a naturally composable system,” Institute
of Science and Technology Austria, 2025.
ista: Wu B. 2025. An examination on phages as a naturally composable system. Institute
of Science and Technology Austria.
mla: Wu, Bryan. An Examination on Phages as a Naturally Composable System.
Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20470.
short: B. Wu, An Examination on Phages as a Naturally Composable System, Institute
of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-10-15T13:30:21Z
date_published: 2025-10-30T00:00:00Z
date_updated: 2026-05-06T08:01:28Z
day: '30'
ddc:
- '579'
degree_awarded: PhD
department:
- _id: GradSch
- _id: CaGu
doi: 10.15479/AT-ISTA-20470
file:
- access_level: closed
checksum: d32ea83f259f6b0506325cd57b1d44c3
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: brwu
date_created: 2025-10-21T17:33:27Z
date_updated: 2026-04-30T22:30:02Z
embargo_to: open_access
file_id: '20516'
file_name: 2025_Wu_Bryan_Thesis.docx
file_size: 10603235
relation: source_file
- access_level: open_access
checksum: 53590046fd3244c5550b4022282449d2
content_type: application/pdf
creator: brwu
date_created: 2025-10-21T17:33:26Z
date_updated: 2026-04-30T22:30:02Z
embargo: 2026-04-30
file_id: '20517'
file_name: 2025_Wu_Bryan_Thesis.pdf
file_size: 6251936
relation: main_file
file_date_updated: 2026-04-30T22:30:02Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '102'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: An examination on phages as a naturally composable system
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
_id: '17325'
abstract:
- lang: eng
text: Bacterial ion fluxes are involved in the generation of energy, transport,
and motility. As such, bacterial electrophysiology is fundamentally important
for the bacterial life cycle, but it is often neglected and consequently, by and
large, not understood. Arguably, the two main reasons for this are the complexity
of measuring relevant variables in small cells with a cell envelope that contains
the cell wall and the fact that, in a unicellular organism, relevant variables
become intertwined in a nontrivial manner. To help give bacterial electrophysiology
studies a firm footing, in this review, we go back to basics. We look first at
the biophysics of bacterial membrane potential, and then at the approaches and
models developed mostly for the study of neurons and eukaryotic mitochondria.
We discuss their applicability to bacterial cells. Finally, we connect bacterial
membrane potential with other relevant (electro)physiological variables and summarize
methods that can be used to both measure and influence bacterial electrophysiology.
acknowledgement: We would like to thank all members of the Pilizota lab, as well as
Calin Guet, Orkun Soyer, Munehiro Asally, Peter Swain, and in particular Matt Scott
and Ariel Amir, for their support, comments, and useful discussions. T.P. and W.-C.L.
were supported by the Leverhulme Trust, grant RPG-2019-187, and T.P. is supported
by EPSRC Fellowship EP/V03264X/1. E.K. was supported by a European Molecular Biology
Organization Long-Term Postdoctoral Fellowship, ALTF 44-2021.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Wei Chang
full_name: Lo, Wei Chang
last_name: Lo
- first_name: Ekaterina
full_name: Krasnopeeva, Ekaterina
id: 1F1EE44A-BF83-11EA-B3C1-BB9CC619BF3A
last_name: Krasnopeeva
- first_name: Teuta
full_name: Pilizota, Teuta
last_name: Pilizota
citation:
ama: Lo WC, Krasnopeeva E, Pilizota T. Bacterial Electrophysiology. Annual Review
of Biophysics. 2024;53:487-510. doi:10.1146/annurev-biophys-030822-032215
apa: Lo, W. C., Krasnopeeva, E., & Pilizota, T. (2024). Bacterial Electrophysiology.
Annual Review of Biophysics. Annual Reviews. https://doi.org/10.1146/annurev-biophys-030822-032215
chicago: Lo, Wei Chang, Ekaterina Krasnopeeva, and Teuta Pilizota. “Bacterial Electrophysiology.”
Annual Review of Biophysics. Annual Reviews, 2024. https://doi.org/10.1146/annurev-biophys-030822-032215.
ieee: W. C. Lo, E. Krasnopeeva, and T. Pilizota, “Bacterial Electrophysiology,”
Annual Review of Biophysics, vol. 53. Annual Reviews, pp. 487–510, 2024.
ista: Lo WC, Krasnopeeva E, Pilizota T. 2024. Bacterial Electrophysiology. Annual
Review of Biophysics. 53, 487–510.
mla: Lo, Wei Chang, et al. “Bacterial Electrophysiology.” Annual Review of Biophysics,
vol. 53, Annual Reviews, 2024, pp. 487–510, doi:10.1146/annurev-biophys-030822-032215.
short: W.C. Lo, E. Krasnopeeva, T. Pilizota, Annual Review of Biophysics 53 (2024)
487–510.
date_created: 2024-07-28T22:01:09Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2025-09-08T08:34:43Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1146/annurev-biophys-030822-032215
external_id:
isi:
- '001278237500021'
pmid:
- '38382113'
file:
- access_level: open_access
checksum: e0505553b3cee624fa865f0cc5a99ecc
content_type: application/pdf
creator: dernst
date_created: 2024-07-29T10:56:01Z
date_updated: 2024-07-29T10:56:01Z
file_id: '17339'
file_name: 2024_AnnualReviewBiophys_Lo.pdf
file_size: 1276645
relation: main_file
success: 1
file_date_updated: 2024-07-29T10:56:01Z
has_accepted_license: '1'
intvolume: ' 53'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 487-510
pmid: 1
project:
- _id: eb872896-77a9-11ec-83b8-f59a38ec17f8
grant_number: ALTF 44-2021
name: 'Bacterial cytoplasm glass transition: passive physiological switch or active
survival strategy'
publication: Annual Review of Biophysics
publication_identifier:
eissn:
- 1936-1238
issn:
- 1936-122X
publication_status: published
publisher: Annual Reviews
quality_controlled: '1'
scopus_import: '1'
status: public
title: Bacterial Electrophysiology
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 53
year: '2024'
...
---
_id: '12478'
abstract:
- lang: eng
text: In Gram negative bacteria, the multiple antibiotic resistance or mar operon,
is known to control the expression of multi-drug efflux genes that protect bacteria
from a wide range of drugs. As many different chemical compounds can induce this
operon, identifying the parameters that govern the dynamics of its induction is
crucial to better characterize the processes of tolerance and resistance. Most
experiments have assumed that the properties of the mar transcriptional network
can be inferred from population measurements. However, measurements from an asynchronous
population of cells can mask underlying phenotypic variations of single cells.
We monitored the activity of the mar promoter in single Escherichia coli cells
in linear micro-colonies and established that the response to a steady level of
inducer was most heterogeneous within individual colonies for an intermediate
value of inducer. Specifically, sub-lineages defined by contiguous daughter-cells
exhibited similar promoter activity, whereas activity was greatly variable between
different sub-lineages. Specific sub-trees of uniform promoter activity persisted
over several generations. Statistical analyses of the lineages suggest that the
presence of these sub-trees is the signature of an inducible memory of the promoter
state that is transmitted from mother to daughter cells. This single-cell study
reveals that the degree of epigenetic inheritance changes as a function of inducer
concentration, suggesting that phenotypic inheritance may be an inducible phenotype.
acknowledgement: This work was supported by NIH P50 award P50GM081892-02 to the University
of Chicago, a catalyst grant from the Chicago Biomedical Consortium with support
from The Searle Funds at The Chicago Community Trust to PC, and a Yen Fellowship
to CCG. MA was partially supported by PAPIIT-UNAM grant IN-11322.
article_number: '1049255'
article_processing_charge: Yes
article_type: original
author:
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: L
full_name: Bruneaux, L
last_name: Bruneaux
- first_name: P
full_name: Oikonomou, P
last_name: Oikonomou
- first_name: M
full_name: Aldana, M
last_name: Aldana
- first_name: P
full_name: Cluzel, P
last_name: Cluzel
citation:
ama: Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. Monitoring lineages of
growing and dividing bacteria reveals an inducible memory of mar operon
expression. Frontiers in Microbiology. 2023;14. doi:10.3389/fmicb.2023.1049255
apa: Guet, C. C., Bruneaux, L., Oikonomou, P., Aldana, M., & Cluzel, P. (2023).
Monitoring lineages of growing and dividing bacteria reveals an inducible memory
of mar operon expression. Frontiers in Microbiology. Frontiers.
https://doi.org/10.3389/fmicb.2023.1049255
chicago: Guet, Calin C, L Bruneaux, P Oikonomou, M Aldana, and P Cluzel. “Monitoring
Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of Mar
Operon Expression.” Frontiers in Microbiology. Frontiers, 2023. https://doi.org/10.3389/fmicb.2023.1049255.
ieee: C. C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, and P. Cluzel, “Monitoring
lineages of growing and dividing bacteria reveals an inducible memory of mar
operon expression,” Frontiers in Microbiology, vol. 14. Frontiers, 2023.
ista: Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. 2023. Monitoring lineages
of growing and dividing bacteria reveals an inducible memory of mar operon
expression. Frontiers in Microbiology. 14, 1049255.
mla: Guet, Calin C., et al. “Monitoring Lineages of Growing and Dividing Bacteria
Reveals an Inducible Memory of Mar Operon Expression.” Frontiers in
Microbiology, vol. 14, 1049255, Frontiers, 2023, doi:10.3389/fmicb.2023.1049255.
short: C.C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, P. Cluzel, Frontiers in
Microbiology 14 (2023).
corr_author: '1'
date_created: 2023-02-02T08:13:28Z
date_published: 2023-06-20T00:00:00Z
date_updated: 2024-10-09T21:03:59Z
day: '20'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.3389/fmicb.2023.1049255
external_id:
isi:
- '001030002600001'
pmid:
- '37485524'
file:
- access_level: open_access
checksum: 7dd322347512afaa5daf72a0154f2f07
content_type: application/pdf
creator: dernst
date_created: 2023-07-31T07:16:34Z
date_updated: 2023-07-31T07:16:34Z
file_id: '13322'
file_name: 2023_FrontiersMicrobiology_Guet.pdf
file_size: 6452841
relation: main_file
success: 1
file_date_updated: 2023-07-31T07:16:34Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Microbiology
publication_identifier:
eissn:
- 1664-302X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Monitoring lineages of growing and dividing bacteria reveals an inducible memory
of mar operon expression
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: 14
year: '2023'
...
---
_id: '11713'
abstract:
- lang: eng
text: "Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF
toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions
at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli.
The MazEF system has been used in various biotechnology and synthetic biology
applications. In this study, we infer how ectopic mazF overexpression affects
production of heterologous proteins. To this end, we quantified the levels of
fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing
or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the
5′-untranslated region of these reporter mRNAs under the same conditions by comparing
expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless
mRNA).\r\nResults: Flow cytometry analysis indicates that during mazF overexpression,
fluorescent proteins are translated from the canonical as well as leaderless mRNAs.
Our analysis further indicates that longer mazF overexpression generally increases
the concentration of fluorescent proteins translated from ACA-less mRNAs, however
it also substantially increases bacterial population heterogeneity. Finally, our
results suggest that the strength and duration of mazF overexpression should be
optimized for each experimental setup, to maximize the heterologous protein production
and minimize the amount of phenotypic heterogeneity in bacterial populations,
which is unfavorable in biotechnological processes."
acknowledgement: "We acknowledge the Max Perutz Labs FACS Facility together with Thomas
Sauer. NN is grateful to Călin C. Guet for his support.\r\nThis work was funded
by the Elise Richter grant V738 of the Austrian Science Fund (FWF), and the FWF
Lise Meitner grant M1697, to NN; and by the FWF grant P22249, FWF Special Research
Program RNA-REG F43 (subproject F4316), and FWF doctoral program RNA Biology (W1207),
to IM. Open access funding provided by the Austrian Science Fund."
article_number: '173'
article_processing_charge: No
article_type: letter_note
author:
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
- first_name: Martina
full_name: Sauert, Martina
last_name: Sauert
- first_name: Tanino G.
full_name: Albanese, Tanino G.
last_name: Albanese
- first_name: Isabella
full_name: Moll, Isabella
last_name: Moll
citation:
ama: Nikolic N, Sauert M, Albanese TG, Moll I. Quantifying heterologous gene expression
during ectopic MazF production in Escherichia coli. BMC Research Notes.
2022;15. doi:10.1186/s13104-022-06061-9
apa: Nikolic, N., Sauert, M., Albanese, T. G., & Moll, I. (2022). Quantifying
heterologous gene expression during ectopic MazF production in Escherichia coli.
BMC Research Notes. Springer Nature. https://doi.org/10.1186/s13104-022-06061-9
chicago: Nikolic, Nela, Martina Sauert, Tanino G. Albanese, and Isabella Moll. “Quantifying
Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.”
BMC Research Notes. Springer Nature, 2022. https://doi.org/10.1186/s13104-022-06061-9.
ieee: N. Nikolic, M. Sauert, T. G. Albanese, and I. Moll, “Quantifying heterologous
gene expression during ectopic MazF production in Escherichia coli,” BMC Research
Notes, vol. 15. Springer Nature, 2022.
ista: Nikolic N, Sauert M, Albanese TG, Moll I. 2022. Quantifying heterologous gene
expression during ectopic MazF production in Escherichia coli. BMC Research Notes.
15, 173.
mla: Nikolic, Nela, et al. “Quantifying Heterologous Gene Expression during Ectopic
MazF Production in Escherichia Coli.” BMC Research Notes, vol. 15, 173,
Springer Nature, 2022, doi:10.1186/s13104-022-06061-9.
short: N. Nikolic, M. Sauert, T.G. Albanese, I. Moll, BMC Research Notes 15 (2022).
corr_author: '1'
date_created: 2022-08-01T09:04:27Z
date_published: 2022-05-13T00:00:00Z
date_updated: 2025-04-14T09:24:53Z
day: '13'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1186/s13104-022-06061-9
external_id:
pmid:
- '35562780'
file:
- access_level: open_access
checksum: 008156e5340e9789f0f6d82bde4d347a
content_type: application/pdf
creator: dernst
date_created: 2022-08-01T09:24:42Z
date_updated: 2022-08-01T09:24:42Z
file_id: '11714'
file_name: 2022_BMCResearchNotes_Nikolic.pdf
file_size: 1545310
relation: main_file
success: 1
file_date_updated: 2022-08-01T09:24:42Z
has_accepted_license: '1'
intvolume: ' 15'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26956E74-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00738
name: Bacterial toxin-antitoxin systems as antiphage defense mechanisms
publication: BMC Research Notes
publication_identifier:
issn:
- 1756-0500
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1186/s13104-022-06152-7
scopus_import: '1'
status: public
title: Quantifying heterologous gene expression during ectopic MazF production in
Escherichia coli
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: 15
year: '2022'
...
---
_id: '11843'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein
located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids
involved in CD14 binding are highly conserved across pathogenic and non-pathogenic
strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration
by overactivation of integrins and blunted expression of co-stimulatory molecules
by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both
rate-limiting factors of T cell activation. This response was binary at the single-cell
level, but averaged in larger populations exposed to both piliated and non-piliated
pathogens, presumably via the exchange of immunomodulatory cytokines. While defining
an active molecular mechanism of immune evasion by pathogens, the interaction
between FimH and CD14 represents a potential target to interfere with persistent
and recurrent infections, such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89,
and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and
Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and
Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific
Service Units, especially the Bioimaging facility, the Preclinical facility and
the Electron microscopy facility for technical support, Jakob Wallner and all members
of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically
reading the manuscript. This work was supported by grants from the Austrian Research
Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373),
and the Austrian Science Fund (FWF P29911) to MS.
article_number: e78995
article_processing_charge: Yes
article_type: original
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
eLife. 2022;11. doi:10.7554/eLife.78995
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.78995
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” ELife. eLife Sciences
Publications, 2022. https://doi.org/10.7554/eLife.78995.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type
1 piliated uropathogenic Escherichia coli hijack the host immune response by binding
to CD14. eLife. 11, e78995.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife
Sciences Publications, 2022, doi:10.7554/eLife.78995.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
ELife 11 (2022).
corr_author: '1'
date_created: 2022-08-14T22:01:46Z
date_published: 2022-07-26T00:00:00Z
date_updated: 2025-04-15T07:17:32Z
day: '26'
ddc:
- '570'
department:
- _id: MiSi
- _id: CaGu
doi: 10.7554/eLife.78995
ec_funded: 1
external_id:
isi:
- '000838410200001'
pmid:
- '35881547'
file:
- access_level: open_access
checksum: 002a3c7c7ea5caa9af9cfbea308f6ea4
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-16T08:57:37Z
date_updated: 2022-08-16T08:57:37Z
file_id: '11861'
file_name: 2022_eLife_Tomasek.pdf
file_size: 2057577
relation: main_file
success: 1
file_date_updated: 2022-08-16T08:57:37Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '10316'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
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: 11
year: '2022'
...
---
_id: '12333'
abstract:
- lang: eng
text: Together, copy-number and point mutations form the basis for most evolutionary
novelty, through the process of gene duplication and divergence. While a plethora
of genomic data reveals the long-term fate of diverging coding sequences and their
cis-regulatory elements, little is known about the early dynamics around the duplication
event itself. In microorganisms, selection for increased gene expression often
drives the expansion of gene copy-number mutations, which serves as a crude adaptation,
prior to divergence through refining point mutations. Using a simple synthetic
genetic reporter system that can distinguish between copy-number and point mutations,
we study their early and transient adaptive dynamics in real time in Escherichia
coli. We find two qualitatively different routes of adaptation, depending on the
level of functional improvement needed. In conditions of high gene expression
demand, the two mutation types occur as a combination. However, under low gene
expression demand, copy-number and point mutations are mutually exclusive; here,
owing to their higher frequency, adaptation is dominated by copy-number mutations,
in a process we term amplification hindrance. Ultimately, due to high reversal
rates and pleiotropic cost, copy-number mutations may not only serve as a crude
and transient adaptation, but also constrain sequence divergence over evolutionary
time scales.
acknowledgement: "We are grateful to N Barton, F Kondrashov, M Lagator, M Pleska,
R Roemhild, D Siekhaus, and G\r\nTkacik for input on the manuscript and to K Tomasek
for help with flow cytometry."
article_number: e82240
article_processing_charge: No
article_type: original
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
- 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: Tomanek I, Guet CC. Adaptation dynamics between copynumber and point mutations.
eLife. 2022;11. doi:10.7554/ELIFE.82240
apa: Tomanek, I., & Guet, C. C. (2022). Adaptation dynamics between copynumber
and point mutations. ELife. eLife Sciences Publications. https://doi.org/10.7554/ELIFE.82240
chicago: Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber
and Point Mutations.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/ELIFE.82240.
ieee: I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point
mutations,” eLife, vol. 11. eLife Sciences Publications, 2022.
ista: Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point
mutations. eLife. 11, e82240.
mla: Tomanek, Isabella, and Calin C. Guet. “Adaptation Dynamics between Copynumber
and Point Mutations.” ELife, vol. 11, e82240, eLife Sciences Publications,
2022, doi:10.7554/ELIFE.82240.
short: I. Tomanek, C.C. Guet, ELife 11 (2022).
corr_author: '1'
date_created: 2023-01-22T23:00:55Z
date_published: 2022-12-22T00:00:00Z
date_updated: 2025-03-06T14:03:50Z
day: '22'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.7554/ELIFE.82240
external_id:
isi:
- '000912674700001'
pmid:
- '36546673'
file:
- access_level: open_access
checksum: 9321fd5f06ff59d5e2d33daee84b3da1
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T08:56:21Z
date_updated: 2023-01-23T08:56:21Z
file_id: '12338'
file_name: 2022_eLife_Tomanek.pdf
file_size: 8835954
relation: main_file
success: 1
file_date_updated: 2023-01-23T08:56:21Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://doi.org/10.5281/zenodo.6974122
record:
- id: '12339'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Adaptation dynamics between copynumber and point mutations
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: 11
year: '2022'
...
---
_id: '12339'
abstract:
- lang: eng
text: 'Copy-number and point mutations form the basis for most evolutionary novelty
through the process of gene duplication and divergence. While a plethora of genomic
sequence data reveals the long-term fate of diverging coding sequences and their
cis-regulatory elements, little is known about the early dynamics around the duplication
event itself. In microorganisms, selection for increased gene expression often
drives the expansion of gene copy-number mutations, which serves as a crude adaptation,
prior to divergence through refining point mutations. Using a simple synthetic
genetic system that allows us to distinguish copy-number and point mutations,
we study their early and transient adaptive dynamics in real-time in Escherichia
coli. We find two qualitatively different routes of adaptation depending on the
level of functional improvement selected for: In conditions of high gene expression
demand, the two types of mutations occur as a combination. Under low gene expression
demand, negative epistasis between the two types of mutations renders them mutually
exclusive. Thus, owing to their higher frequency, adaptation is dominated by copy-number
mutations. Ultimately, due to high rates of reversal and pleiotropic cost, copy-number
mutations may not only serve as a crude and transient adaptation but also constrain
sequence divergence over evolutionary time scales.'
article_processing_charge: No
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
- 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: Tomanek I, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data
of populations evolving in galactose. 2022. doi:10.5061/dryad.rfj6q57ds
apa: Tomanek, I., & Guet, C. C. (2022). Flow cytometry YFP and CFP data and
deep sequencing data of populations evolving in galactose. Dryad. https://doi.org/10.5061/dryad.rfj6q57ds
chicago: Tomanek, Isabella, and Calin C Guet. “Flow Cytometry YFP and CFP Data and
Deep Sequencing Data of Populations Evolving in Galactose.” Dryad, 2022. https://doi.org/10.5061/dryad.rfj6q57ds.
ieee: I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing
data of populations evolving in galactose.” Dryad, 2022.
ista: Tomanek I, Guet CC. 2022. Flow cytometry YFP and CFP data and deep sequencing
data of populations evolving in galactose, Dryad, 10.5061/dryad.rfj6q57ds.
mla: Tomanek, Isabella, and Calin C. Guet. Flow Cytometry YFP and CFP Data and
Deep Sequencing Data of Populations Evolving in Galactose. Dryad, 2022, doi:10.5061/dryad.rfj6q57ds.
short: I. Tomanek, C.C. Guet, (2022).
corr_author: '1'
date_created: 2023-01-23T09:00:37Z
date_published: 2022-12-23T00:00:00Z
date_updated: 2025-03-06T14:03:50Z
day: '23'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.5061/dryad.rfj6q57ds
main_file_link:
- open_access: '1'
url: https://doi.org/10.5061/dryad.rfj6q57ds
month: '12'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
record:
- id: '12333'
relation: used_in_publication
status: public
status: public
title: Flow cytometry YFP and CFP data and deep sequencing data of populations evolving
in galactose
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '10736'
abstract:
- lang: eng
text: Predicting function from sequence is a central problem of biology. Currently,
this is possible only locally in a narrow mutational neighborhood around a wildtype
sequence rather than globally from any sequence. Using random mutant libraries,
we developed a biophysical model that accounts for multiple features of σ70 binding
bacterial promoters to predict constitutive gene expression levels from any sequence.
We experimentally and theoretically estimated that 10–20% of random sequences
lead to expression and ~80% of non-expressing sequences are one mutation away
from a functional promoter. The potential for generating expression from random
sequences is so pervasive that selection acts against σ70-RNA polymerase binding
sites even within inter-genic, promoter-containing regions. This pervasiveness
of σ70-binding sites implies that emergence of promoters is not the limiting step
in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter
function into a mechanistic model enabled not only more accurate predictions of
gene expression levels, but also identified that promoters evolve more rapidly
than previously thought.
acknowledgement: 'We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao,
Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on
the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded
by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML;
IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme
7 (2007–2013, grant agreement number 648440) to JPB.'
article_number: e64543
article_processing_charge: No
article_type: original
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Srdjan
full_name: Sarikas, Srdjan
id: 35F0286E-F248-11E8-B48F-1D18A9856A87
last_name: Sarikas
- first_name: Magdalena
full_name: Steinrück, Magdalena
id: 2C023F40-F248-11E8-B48F-1D18A9856A87
last_name: Steinrück
orcid: 0000-0003-1229-9719
- first_name: David
full_name: Toledo-Aparicio, David
last_name: Toledo-Aparicio
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Lagator M, Sarikas S, Steinrück M, et al. Predicting bacterial promoter function
and evolution from random sequences. eLife. 2022;11. doi:10.7554/eLife.64543
apa: Lagator, M., Sarikas, S., Steinrück, M., Toledo-Aparicio, D., Bollback, J.
P., Guet, C. C., & Tkačik, G. (2022). Predicting bacterial promoter function
and evolution from random sequences. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.64543
chicago: Lagator, Mato, Srdjan Sarikas, Magdalena Steinrück, David Toledo-Aparicio,
Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter
Function and Evolution from Random Sequences.” ELife. eLife Sciences Publications,
2022. https://doi.org/10.7554/eLife.64543.
ieee: M. Lagator et al., “Predicting bacterial promoter function and evolution
from random sequences,” eLife, vol. 11. eLife Sciences Publications, 2022.
ista: Lagator M, Sarikas S, Steinrück M, Toledo-Aparicio D, Bollback JP, Guet CC,
Tkačik G. 2022. Predicting bacterial promoter function and evolution from random
sequences. eLife. 11, e64543.
mla: Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution
from Random Sequences.” ELife, vol. 11, e64543, eLife Sciences Publications,
2022, doi:10.7554/eLife.64543.
short: M. Lagator, S. Sarikas, M. Steinrück, D. Toledo-Aparicio, J.P. Bollback,
C.C. Guet, G. Tkačik, ELife 11 (2022).
corr_author: '1'
date_created: 2022-02-06T23:01:32Z
date_published: 2022-01-26T00:00:00Z
date_updated: 2025-03-31T16:00:23Z
day: '26'
ddc:
- '576'
department:
- _id: CaGu
- _id: GaTk
- _id: NiBa
doi: 10.7554/eLife.64543
ec_funded: 1
external_id:
isi:
- '000751104400001'
pmid:
- '35080492'
file:
- access_level: open_access
checksum: decdcdf600ff51e9a9703b49ca114170
content_type: application/pdf
creator: cchlebak
date_created: 2022-02-07T07:14:09Z
date_updated: 2022-02-07T07:14:09Z
file_id: '10739'
file_name: 2022_ELife_Lagator.pdf
file_size: 5604343
relation: main_file
success: 1
file_date_updated: 2022-02-07T07:14:09Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '648440'
name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Predicting bacterial promoter function and evolution from random sequences
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: 11
year: '2022'
...
---
_id: '10812'
abstract:
- lang: eng
text: Several promising strategies based on combining or cycling different antibiotics
have been proposed to increase efficacy and counteract resistance evolution, but
we still lack a deep understanding of the physiological responses and genetic
mechanisms that underlie antibiotic interactions and the clinical applicability
of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological
stress responses and emerging resistance mutations (occurring at different time
scales) generate complex and often unpredictable dynamics. In this Review, we
present our current understanding of bacterial cell physiology and genetics of
responses to antibiotics. We emphasize recently discovered mechanisms of synergistic
and antagonistic drug interactions, hysteresis in temporal interactions between
antibiotics that arise from microbial physiology and interactions between antibiotics
and resistance mutations that can cause collateral sensitivity or cross-resistance.
We discuss possible connections between the different phenomena and indicate relevant
research directions. A better and more unified understanding of drug and genetic
interactions is likely to advance antibiotic therapy.
acknowledgement: The authors thank B. Kavčič and H. Schulenburg for constructive feedback
on the manuscript.
article_processing_charge: No
article_type: review
author:
- first_name: Roderich
full_name: Römhild, Roderich
id: 68E56E44-62B0-11EA-B963-444F3DDC885E
last_name: Römhild
orcid: 0000-0001-9480-5261
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
- first_name: Dan I.
full_name: Andersson, Dan I.
last_name: Andersson
citation:
ama: Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial
responses to antibiotic combinations. Nature Reviews Microbiology. 2022;20:478-490.
doi:10.1038/s41579-022-00700-5
apa: Römhild, R., Bollenbach, M. T., & Andersson, D. I. (2022). The physiology
and genetics of bacterial responses to antibiotic combinations. Nature Reviews
Microbiology. Springer Nature. https://doi.org/10.1038/s41579-022-00700-5
chicago: Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology
and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews
Microbiology. Springer Nature, 2022. https://doi.org/10.1038/s41579-022-00700-5.
ieee: R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics
of bacterial responses to antibiotic combinations,” Nature Reviews Microbiology,
vol. 20. Springer Nature, pp. 478–490, 2022.
ista: Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics
of bacterial responses to antibiotic combinations. Nature Reviews Microbiology.
20, 478–490.
mla: Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses
to Antibiotic Combinations.” Nature Reviews Microbiology, vol. 20, Springer
Nature, 2022, pp. 478–90, doi:10.1038/s41579-022-00700-5.
short: R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology
20 (2022) 478–490.
date_created: 2022-03-04T04:33:49Z
date_published: 2022-08-01T00:00:00Z
date_updated: 2023-08-02T14:41:44Z
day: '01'
department:
- _id: CaGu
doi: 10.1038/s41579-022-00700-5
external_id:
isi:
- '000763891900001'
pmid:
- '35241807'
intvolume: ' 20'
isi: 1
keyword:
- General Immunology and Microbiology
- Microbiology
- Infectious Diseases
language:
- iso: eng
month: '08'
oa_version: None
page: 478-490
pmid: 1
publication: Nature Reviews Microbiology
publication_identifier:
eissn:
- 1740-1534
issn:
- 1740-1526
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: The physiology and genetics of bacterial responses to antibiotic combinations
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 20
year: '2022'
...
---
_id: '10939'
abstract:
- lang: eng
text: Understanding and characterising biochemical processes inside single cells
requires experimental platforms that allow one to perturb and observe the dynamics
of such processes as well as computational methods to build and parameterise models
from the collected data. Recent progress with experimental platforms and optogenetics
has made it possible to expose each cell in an experiment to an individualised
input and automatically record cellular responses over days with fine time resolution.
However, methods to infer parameters of stochastic kinetic models from single-cell
longitudinal data have generally been developed under the assumption that experimental
data is sparse and that responses of cells to at most a few different input perturbations
can be observed. Here, we investigate and compare different approaches for calculating
parameter likelihoods of single-cell longitudinal data based on approximations
of the chemical master equation (CME) with a particular focus on coupling the
linear noise approximation (LNA) or moment closure methods to a Kalman filter.
We show that, as long as cells are measured sufficiently frequently, coupling
the LNA to a Kalman filter allows one to accurately approximate likelihoods and
to infer model parameters from data even in cases where the LNA provides poor
approximations of the CME. Furthermore, the computational cost of filtering-based
iterative likelihood evaluation scales advantageously in the number of measurement
times and different input perturbations and is thus ideally suited for data obtained
from modern experimental platforms. To demonstrate the practical usefulness of
these results, we perform an experiment in which single cells, equipped with an
optogenetic gene expression system, are exposed to various different light-input
sequences and measured at several hundred time points and use parameter inference
based on iterative likelihood evaluation to parameterise a stochastic model of
the system.
acknowledgement: We thank Virgile Andreani for useful discussions about the model
and parameter inference. We thank Johan Paulsson and Jeffrey J Tabor for kind gifts
of plasmids. R was supported by the ANR grant CyberCircuits (ANR-18-CE91-0002).
The funders had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
article_number: e1009950
article_processing_charge: No
article_type: original
author:
- first_name: Anđela
full_name: Davidović, Anđela
last_name: Davidović
- first_name: Remy P
full_name: Chait, Remy P
id: 3464AE84-F248-11E8-B48F-1D18A9856A87
last_name: Chait
orcid: 0000-0003-0876-3187
- first_name: Gregory
full_name: Batt, Gregory
last_name: Batt
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
citation:
ama: Davidović A, Chait RP, Batt G, Ruess J. Parameter inference for stochastic
biochemical models from perturbation experiments parallelised at the single cell
level. PLoS Computational Biology. 2022;18(3). doi:10.1371/journal.pcbi.1009950
apa: Davidović, A., Chait, R. P., Batt, G., & Ruess, J. (2022). Parameter inference
for stochastic biochemical models from perturbation experiments parallelised at
the single cell level. PLoS Computational Biology. Public Library of Science.
https://doi.org/10.1371/journal.pcbi.1009950
chicago: Davidović, Anđela, Remy P Chait, Gregory Batt, and Jakob Ruess. “Parameter
Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised
at the Single Cell Level.” PLoS Computational Biology. Public Library of
Science, 2022. https://doi.org/10.1371/journal.pcbi.1009950.
ieee: A. Davidović, R. P. Chait, G. Batt, and J. Ruess, “Parameter inference for
stochastic biochemical models from perturbation experiments parallelised at the
single cell level,” PLoS Computational Biology, vol. 18, no. 3. Public
Library of Science, 2022.
ista: Davidović A, Chait RP, Batt G, Ruess J. 2022. Parameter inference for stochastic
biochemical models from perturbation experiments parallelised at the single cell
level. PLoS Computational Biology. 18(3), e1009950.
mla: Davidović, Anđela, et al. “Parameter Inference for Stochastic Biochemical Models
from Perturbation Experiments Parallelised at the Single Cell Level.” PLoS
Computational Biology, vol. 18, no. 3, e1009950, Public Library of Science,
2022, doi:10.1371/journal.pcbi.1009950.
short: A. Davidović, R.P. Chait, G. Batt, J. Ruess, PLoS Computational Biology 18
(2022).
date_created: 2022-04-03T22:01:42Z
date_published: 2022-03-18T00:00:00Z
date_updated: 2025-09-09T14:29:53Z
day: '18'
ddc:
- '570'
- '000'
department:
- _id: CaGu
doi: 10.1371/journal.pcbi.1009950
external_id:
isi:
- '001044208400004'
pmid:
- '35303737'
file:
- access_level: open_access
checksum: 458ef542761fb714ced214f240daf6b2
content_type: application/pdf
creator: dernst
date_created: 2022-04-04T10:14:39Z
date_updated: 2022-04-04T10:14:39Z
file_id: '10947'
file_name: 2022_PLoSCompBio_Davidovic.pdf
file_size: 2958642
relation: main_file
success: 1
file_date_updated: 2022-04-04T10:14:39Z
has_accepted_license: '1'
intvolume: ' 18'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLoS Computational Biology
publication_identifier:
eissn:
- 1553-7358
issn:
- 1553-734X
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://gitlab.pasteur.fr/adavidov/inferencelnakf
scopus_import: '1'
status: public
title: Parameter inference for stochastic biochemical models from perturbation experiments
parallelised at the single cell level
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 18
year: '2022'
...
---
_id: '11339'
abstract:
- lang: eng
text: The interaction between a cell and its environment shapes fundamental intracellular
processes such as cellular metabolism. In most cases growth rate is treated as
a proximal metric for understanding the cellular metabolic status. However, changes
in growth rate might not reflect metabolic variations in individuals responding
to environmental fluctuations. Here we use single-cell microfluidics-microscopy
combined with transcriptomics, proteomics and mathematical modelling to quantify
the accumulation of glucose within Escherichia coli cells. In contrast to the
current consensus, we reveal that environmental conditions which are comparatively
unfavourable for growth, where both nutrients and salinity are depleted, increase
glucose accumulation rates in individual bacteria and population subsets. We find
that these changes in metabolic function are underpinned by variations at the
translational and posttranslational level but not at the transcriptional level
and are not dictated by changes in cell size. The metabolic response-characteristics
identified greatly advance our fundamental understanding of the interactions between
bacteria and their environment and have important ramifications when investigating
cellular processes where salinity plays an important role.
acknowledgement: G.G. was supported by an EPSRC DTP PhD studentship (EP/M506527/1).
M.V. and K.T.A. gratefully acknowledge financial support from the EPSRC (EP/N014391/1).
U.L. was supported through a BBSRC grant (BB/V008021/1) and an MRC Proximity to
Discovery EXCITEME2 grant (MCPC17189). This work was further supported by a Royal
Society Research Grant (RG180007) awarded to S.P. and a QUEX Initiator grant awarded
to S.P. and K.T.A.. D.S.M., T.A.R. and S.P.’s work in this area is also supported
by a Marie Skłodowska-Curie project SINGEK (H2020-MSCA-ITN-2015-675752) and the
Gordon and Betty Moore Foundation Marine Microbiology Initiative (GBMF5514). B.M.I.
acknowledges support from a Wellcome Trust Institutional Strategic Support Award
to the University of Exeter (204909/Z/16/Z). This project utilised equipment funded
by the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome
Trust Multi User Equipment Award (WT101650MA) and BBSRC LOLA award (BB/K003240/1).
article_number: '385'
article_processing_charge: No
article_type: original
author:
- first_name: Georgina
full_name: Glover, Georgina
last_name: Glover
- first_name: Margaritis
full_name: Voliotis, Margaritis
last_name: Voliotis
- first_name: Urszula
full_name: Łapińska, Urszula
last_name: Łapińska
- first_name: Brandon M.
full_name: Invergo, Brandon M.
last_name: Invergo
- first_name: Darren
full_name: Soanes, Darren
last_name: Soanes
- first_name: Paul
full_name: O’Neill, Paul
last_name: O’Neill
- first_name: Karen
full_name: Moore, Karen
last_name: Moore
- first_name: Nela
full_name: Nikolic, Nela
id: 42D9CABC-F248-11E8-B48F-1D18A9856A87
last_name: Nikolic
orcid: 0000-0001-9068-6090
- first_name: Peter
full_name: Petrov, Peter
last_name: Petrov
- first_name: David S.
full_name: Milner, David S.
last_name: Milner
- first_name: Sumita
full_name: Roy, Sumita
last_name: Roy
- first_name: Kate
full_name: Heesom, Kate
last_name: Heesom
- first_name: Thomas A.
full_name: Richards, Thomas A.
last_name: Richards
- first_name: Krasimira
full_name: Tsaneva-Atanasova, Krasimira
last_name: Tsaneva-Atanasova
- first_name: Stefano
full_name: Pagliara, Stefano
last_name: Pagliara
citation:
ama: Glover G, Voliotis M, Łapińska U, et al. Nutrient and salt depletion synergistically
boosts glucose metabolism in individual Escherichia coli cells. Communications
Biology. 2022;5. doi:10.1038/s42003-022-03336-6
apa: Glover, G., Voliotis, M., Łapińska, U., Invergo, B. M., Soanes, D., O’Neill,
P., … Pagliara, S. (2022). Nutrient and salt depletion synergistically boosts
glucose metabolism in individual Escherichia coli cells. Communications Biology.
Springer Nature. https://doi.org/10.1038/s42003-022-03336-6
chicago: Glover, Georgina, Margaritis Voliotis, Urszula Łapińska, Brandon M. Invergo,
Darren Soanes, Paul O’Neill, Karen Moore, et al. “Nutrient and Salt Depletion
Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.”
Communications Biology. Springer Nature, 2022. https://doi.org/10.1038/s42003-022-03336-6.
ieee: G. Glover et al., “Nutrient and salt depletion synergistically boosts
glucose metabolism in individual Escherichia coli cells,” Communications Biology,
vol. 5. Springer Nature, 2022.
ista: Glover G, Voliotis M, Łapińska U, Invergo BM, Soanes D, O’Neill P, Moore K,
Nikolic N, Petrov P, Milner DS, Roy S, Heesom K, Richards TA, Tsaneva-Atanasova
K, Pagliara S. 2022. Nutrient and salt depletion synergistically boosts glucose
metabolism in individual Escherichia coli cells. Communications Biology. 5, 385.
mla: Glover, Georgina, et al. “Nutrient and Salt Depletion Synergistically Boosts
Glucose Metabolism in Individual Escherichia Coli Cells.” Communications Biology,
vol. 5, 385, Springer Nature, 2022, doi:10.1038/s42003-022-03336-6.
short: G. Glover, M. Voliotis, U. Łapińska, B.M. Invergo, D. Soanes, P. O’Neill,
K. Moore, N. Nikolic, P. Petrov, D.S. Milner, S. Roy, K. Heesom, T.A. Richards,
K. Tsaneva-Atanasova, S. Pagliara, Communications Biology 5 (2022).
date_created: 2022-05-01T22:01:41Z
date_published: 2022-04-20T00:00:00Z
date_updated: 2023-08-03T06:45:26Z
day: '20'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1038/s42003-022-03336-6
external_id:
isi:
- '000784143400001'
pmid:
- '35444215'
file:
- access_level: open_access
checksum: 7c6f76ab17393d650825cc240edc84b3
content_type: application/pdf
creator: dernst
date_created: 2022-05-02T06:26:26Z
date_updated: 2022-05-02T06:26:26Z
file_id: '11342'
file_name: 2022_CommBiology_Glover.pdf
file_size: 2827723
relation: main_file
success: 1
file_date_updated: 2022-05-02T06:26:26Z
has_accepted_license: '1'
intvolume: ' 5'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Communications Biology
publication_identifier:
eissn:
- 2399-3642
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nutrient and salt depletion synergistically boosts glucose metabolism in individual
Escherichia coli cells
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 5
year: '2022'
...