---
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
license: https://creativecommons.org/licenses/by/4.0/
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'
...
---
_id: '9786'
article_processing_charge: No
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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: Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text
and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting
Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.”
Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public
Library of Science, 10.1371/journal.pcbi.1007168.s001.
mla: Ruess, Jakob, et al. Supporting Text and Results. Public Library of
Science, 2019, doi:10.1371/journal.pcbi.1007168.s001.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).
date_created: 2021-08-06T08:23:43Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2025-04-15T07:33:55Z
day: '02'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168.s001
month: '07'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '6784'
relation: used_in_publication
status: public
status: public
title: Supporting text and results
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2019'
...
---
_id: '6784'
abstract:
- lang: eng
text: Mathematical models have been used successfully at diverse scales of biological
organization, ranging from ecology and population dynamics to stochastic reaction
events occurring between individual molecules in single cells. Generally, many
biological processes unfold across multiple scales, with mutations being the best
studied example of how stochasticity at the molecular scale can influence outcomes
at the population scale. In many other contexts, however, an analogous link between
micro- and macro-scale remains elusive, primarily due to the challenges involved
in setting up and analyzing multi-scale models. Here, we employ such a model to
investigate how stochasticity propagates from individual biochemical reaction
events in the bacterial innate immune system to the ecology of bacteria and bacterial
viruses. We show analytically how the dynamics of bacterial populations are shaped
by the activities of immunity-conferring enzymes in single cells and how the ecological
consequences imply optimal bacterial defense strategies against viruses. Our results
suggest that bacterial populations in the presence of viruses can either optimize
their initial growth rate or their population size, with the first strategy favoring
simple immunity featuring a single restriction modification system and the second
strategy favoring complex bacterial innate immunity featuring several simultaneously
active restriction modification systems.
article_number: e1007168
article_processing_charge: No
article_type: original
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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: Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes
bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise
of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology.
Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular
Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational
Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate
immunity shapes bacteria-phage ecologies,” PLoS Computational Biology,
vol. 15, no. 7. Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity
shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168.
mla: Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage
Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public
Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15
(2019).
date_created: 2019-08-11T21:59:19Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2025-04-14T13:46:26Z
day: '02'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168
external_id:
isi:
- '000481577700032'
file:
- access_level: open_access
checksum: 7ded4721b41c2a0fc66a1c634540416a
content_type: application/pdf
creator: dernst
date_created: 2019-08-12T12:27:26Z
date_updated: 2020-07-14T12:47:40Z
file_id: '6803'
file_name: 2019_PlosComputBiology_Ruess.pdf
file_size: 2200003
relation: main_file
file_date_updated: 2020-07-14T12:47:40Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
grant_number: '24210'
name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
at the Single-Cell Level
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
Systems
publication: PLoS Computational Biology
publication_identifier:
eissn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '9786'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Molecular noise of innate immunity shapes bacteria-phage ecologies
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: 15
year: '2019'
...
---
_id: '82'
abstract:
- lang: eng
text: In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage,
bacterial cells resistant to the phage commonly emerge and become the dominant
population of bacteria. Following the ascent of resistant mutants, the densities
of bacteria in these simple communities become limited by resources rather than
the phage. Despite the evolution of resistant hosts, upon which the phage cannot
replicate, the lytic phage population is most commonly maintained in an apparently
stable state with the resistant bacteria. Several mechanisms have been put forward
to account for this result. Here we report the results of population dynamic/evolution
experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli
in serial transfer cultures. We show that, following the ascent of λVIR-resistant
bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal
media and in all cases in nutrient-rich broth. Using mathematical models and experiments,
we show that the dominant mechanism responsible for maintenance of λVIRin these
resource-limited populations dominated by resistant E. coli is a high rate of
either phenotypic or genetic transition from resistance to susceptibility—a hitherto
undemonstrated mechanism we term "leaky resistance." We discuss the
implications of leaky resistance to our understanding of the conditions for the
maintenance of phage in populations of bacteria—their “existence conditions.”.
article_number: '2005971'
article_processing_charge: Yes
author:
- first_name: Waqas
full_name: Chaudhry, Waqas
last_name: Chaudhry
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Nilang
full_name: Shah, Nilang
last_name: Shah
- first_name: Howard
full_name: Weiss, Howard
last_name: Weiss
- first_name: Ingrid
full_name: Mccall, Ingrid
last_name: Mccall
- first_name: Justin
full_name: Meyer, Justin
last_name: Meyer
- first_name: Animesh
full_name: Gupta, Animesh
last_name: Gupta
- 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: Bruce
full_name: Levin, Bruce
last_name: Levin
citation:
ama: Chaudhry W, Pleska M, Shah N, et al. Leaky resistance and the conditions for
the existence of lytic bacteriophage. PLoS Biology. 2018;16(8). doi:10.1371/journal.pbio.2005971
apa: Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin,
B. (2018). Leaky resistance and the conditions for the existence of lytic bacteriophage.
PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971
chicago: Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall,
Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Leaky Resistance
and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology.
Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.
ieee: W. Chaudhry et al., “Leaky resistance and the conditions for the existence
of lytic bacteriophage,” PLoS Biology, vol. 16, no. 8. Public Library of
Science, 2018.
ista: Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC,
Levin B. 2018. Leaky resistance and the conditions for the existence of lytic
bacteriophage. PLoS Biology. 16(8), 2005971.
mla: Chaudhry, Waqas, et al. “Leaky Resistance and the Conditions for the Existence
of Lytic Bacteriophage.” PLoS Biology, vol. 16, no. 8, 2005971, Public
Library of Science, 2018, doi:10.1371/journal.pbio.2005971.
short: W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta,
C.C. Guet, B. Levin, PLoS Biology 16 (2018).
date_created: 2018-12-11T11:44:32Z
date_published: 2018-08-16T00:00:00Z
date_updated: 2023-09-13T08:45:41Z
day: '16'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.pbio.2005971
external_id:
isi:
- '000443383300024'
file:
- access_level: open_access
checksum: 527076f78265cd4ea192cd1569851587
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T12:55:31Z
date_updated: 2020-07-14T12:48:10Z
file_id: '5706'
file_name: 2018_Plos_Chaudhry.pdf
file_size: 4007095
relation: main_file
file_date_updated: 2020-07-14T12:48:10Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
publication: PLoS Biology
publication_status: published
publisher: Public Library of Science
publist_id: '7972'
quality_controlled: '1'
related_material:
record:
- id: '9810'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Leaky resistance and the conditions for the existence of lytic bacteriophage
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 16
year: '2018'
...
---
_id: '9810'
article_processing_charge: No
author:
- first_name: Waqas
full_name: Chaudhry, Waqas
last_name: Chaudhry
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Nilang
full_name: Shah, Nilang
last_name: Shah
- first_name: Howard
full_name: Weiss, Howard
last_name: Weiss
- first_name: Ingrid
full_name: Mccall, Ingrid
last_name: Mccall
- first_name: Justin
full_name: Meyer, Justin
last_name: Meyer
- first_name: Animesh
full_name: Gupta, Animesh
last_name: Gupta
- 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: Bruce
full_name: Levin, Bruce
last_name: Levin
citation:
ama: Chaudhry W, Pleska M, Shah N, et al. Numerical data used in figures. 2018.
doi:10.1371/journal.pbio.2005971.s008
apa: Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin,
B. (2018). Numerical data used in figures. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971.s008
chicago: Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall,
Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Numerical Data Used
in Figures.” Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.s008.
ieee: W. Chaudhry et al., “Numerical data used in figures.” Public Library
of Science, 2018.
ista: Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC,
Levin B. 2018. Numerical data used in figures, Public Library of Science, 10.1371/journal.pbio.2005971.s008.
mla: Chaudhry, Waqas, et al. Numerical Data Used in Figures. Public Library
of Science, 2018, doi:10.1371/journal.pbio.2005971.s008.
short: W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta,
C.C. Guet, B. Levin, (2018).
date_created: 2021-08-06T12:43:44Z
date_published: 2018-08-16T00:00:00Z
date_updated: 2023-09-13T08:45:41Z
day: '16'
department:
- _id: CaGu
doi: 10.1371/journal.pbio.2005971.s008
month: '08'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '82'
relation: used_in_publication
status: public
status: public
title: Numerical data used in figures
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2018'
...
---
_id: '457'
abstract:
- lang: eng
text: Temperate bacteriophages integrate in bacterial genomes as prophages and represent
an important source of genetic variation for bacterial evolution, frequently transmitting
fitness-augmenting genes such as toxins responsible for virulence of major pathogens.
However, only a fraction of bacteriophage infections are lysogenic and lead to
prophage acquisition, whereas the majority are lytic and kill the infected bacteria.
Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity
to bacteriophages are expected to act as a double-edged sword and increase the
odds of survival at the cost of depriving bacteria of potentially beneficial prophages.
We show that although restriction-modification systems as mechanisms of innate
immunity prevent both lytic and lysogenic infections indiscriminately in individual
bacteria, they increase the number of prophage-acquiring individuals at the population
level. We find that this counterintuitive result is a consequence of phage-host
population dynamics, in which restriction-modification systems delay infection
onset until bacteria reach densities at which the probability of lysogeny increases.
These results underscore the importance of population-level dynamics as a key
factor modulating costs and benefits of immunity to temperate bacteriophages
article_processing_charge: No
author:
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Dominik
full_name: Refardt, Dominik
last_name: Refardt
- first_name: Bruce
full_name: Levin, Bruce
last_name: Levin
- 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: Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics
promotes prophage acquisition in bacteria with innate immunity. Nature Ecology
and Evolution. 2018;2(2):359-366. doi:10.1038/s41559-017-0424-z
apa: Pleska, M., Lang, M., Refardt, D., Levin, B., & Guet, C. C. (2018). Phage-host
population dynamics promotes prophage acquisition in bacteria with innate immunity.
Nature Ecology and Evolution. Springer Nature. https://doi.org/10.1038/s41559-017-0424-z
chicago: Pleska, Maros, Moritz Lang, Dominik Refardt, Bruce Levin, and Calin C Guet.
“Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with
Innate Immunity.” Nature Ecology and Evolution. Springer Nature, 2018.
https://doi.org/10.1038/s41559-017-0424-z.
ieee: M. Pleska, M. Lang, D. Refardt, B. Levin, and C. C. Guet, “Phage-host population
dynamics promotes prophage acquisition in bacteria with innate immunity,” Nature
Ecology and Evolution, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018.
ista: Pleska M, Lang M, Refardt D, Levin B, Guet CC. 2018. Phage-host population
dynamics promotes prophage acquisition in bacteria with innate immunity. Nature
Ecology and Evolution. 2(2), 359–366.
mla: Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition
in Bacteria with Innate Immunity.” Nature Ecology and Evolution, vol. 2,
no. 2, Springer Nature, 2018, pp. 359–66, doi:10.1038/s41559-017-0424-z.
short: M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution
2 (2018) 359–366.
corr_author: '1'
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date_updated: 2026-04-08T14:19:43Z
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- _id: GaTk
doi: 10.1038/s41559-017-0424-z
ec_funded: 1
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issue: '2'
language:
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month: '02'
oa_version: None
page: 359 - 366
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
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text: information on culture conditions, phage mutagenesis, verification and lysate
preparation; Raw data
article_processing_charge: No
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full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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: Pleska M, Guet CC. Supplementary materials and methods; Full data set from
effects of mutations in phage restriction sites during escape from restriction–modification.
2017. doi:10.6084/m9.figshare.5633917.v1
apa: Pleska, M., & Guet, C. C. (2017). Supplementary materials and methods;
Full data set from effects of mutations in phage restriction sites during escape
from restriction–modification. The Royal Society. https://doi.org/10.6084/m9.figshare.5633917.v1
chicago: Pleska, Maros, and Calin C Guet. “Supplementary Materials and Methods;
Full Data Set from Effects of Mutations in Phage Restriction Sites during Escape
from Restriction–Modification.” The Royal Society, 2017. https://doi.org/10.6084/m9.figshare.5633917.v1.
ieee: M. Pleska and C. C. Guet, “Supplementary materials and methods; Full data
set from effects of mutations in phage restriction sites during escape from restriction–modification.”
The Royal Society, 2017.
ista: Pleska M, Guet CC. 2017. Supplementary materials and methods; Full data set
from effects of mutations in phage restriction sites during escape from restriction–modification,
The Royal Society, 10.6084/m9.figshare.5633917.v1.
mla: Pleska, Maros, and Calin C. Guet. Supplementary Materials and Methods; Full
Data Set from Effects of Mutations in Phage Restriction Sites during Escape from
Restriction–Modification. The Royal Society, 2017, doi:10.6084/m9.figshare.5633917.v1.
short: M. Pleska, C.C. Guet, (2017).
corr_author: '1'
date_created: 2021-08-09T13:54:38Z
date_published: 2017-11-27T00:00:00Z
date_updated: 2025-09-11T07:42:21Z
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...
---
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abstract:
- lang: eng
text: 'Restriction-modification (RM) represents the simplest and possibly the most
widespread mechanism of self/non-self discrimination in nature. In order to provide
bacteria with immunity against bacteriophages and other parasitic genetic elements,
RM systems rely on a balance between two enzymes: the restriction enzyme, which
cleaves non-self DNA at specific restriction sites, and the modification enzyme,
which tags the host’s DNA as self and thus protects it from cleavage. In this
thesis, I use population and single-cell level experiments in combination with
mathematical modeling to study different aspects of the interplay between RM systems,
bacteria and bacteriophages. First, I analyze how mutations in phage restriction
sites affect the probability of phage escape – an inherently stochastic process,
during which phages accidently get modified instead of restricted. Next, I use
single-cell experiments to show that RM systems can, with a low probability, attack
the genome of their bacterial host and that this primitive form of autoimmunity
leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally,
I investigate the nature of interactions between bacteria, RM systems and temperate
bacteriophages to find that, as a consequence of phage escape and its impact on
population dynamics, RM systems can promote acquisition of symbiotic bacteriophages,
rather than limit it. The results presented here uncover new fundamental biological
properties of RM systems and highlight their importance in the ecology and evolution
of bacteria, bacteriophages and their interactions.'
acknowledgement: "During my PhD studies, I received help from many people, all of
which unfortunately cannot be listed here. I thank them deeply and hope that I never
made them regret their kindness.\r\nI would like to express my deepest gratitude
to Călin Guet, who went far beyond his responsibilities as an advisor and was to
me also a great mentor and a friend. Călin never questioned my potential or lacked
compassion and I cannot thank him enough for cultivating in me an independent scientist.
I was amazed by his ability to recognize the most fascinating scientific problems
in objects of study that others would find mundane. I hope I adopted at least a
fraction of this ability.\r\nI will be forever grateful to Bruce Levin for all his
support and especially for giving me the best possible example of how one can practice
excellent science with humor and style. Working with Bruce was a true privilege.\r\nI
thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the
Austrian Academy of Science for funding my PhD research via the DOC fellowship.\r\nI
thank all our lab members: Tobias Bergmiller for his guidance, especially in the
first years of my research, and for being a good friend throughout; Remy Chait for
staying in the lab at unreasonable hours and for the good laughs at bad jokes we
shared; Anna Staron for supportively listening to my whines whenever I had to run
a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for
keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek
for always being nice to me, no matter how much bench space I took from her.\r\nI
thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing
the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics
analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical
modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts.\r\nFinally,
I would like to thank my family and especially my wife Edita, who sacrificed a lot
so that I can pursue my goals and dreams.\r\n"
alternative_title:
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author:
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full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
citation:
ama: Pleska M. Biology of restriction-modification systems at the single-cell and
population level. 2017. doi:10.15479/AT:ISTA:th_916
apa: Pleska, M. (2017). Biology of restriction-modification systems at the single-cell
and population level. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_916
chicago: Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell
and Population Level.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_916.
ieee: M. Pleska, “Biology of restriction-modification systems at the single-cell
and population level,” Institute of Science and Technology Austria, 2017.
ista: Pleska M. 2017. Biology of restriction-modification systems at the single-cell
and population level. Institute of Science and Technology Austria.
mla: Pleska, Maros. Biology of Restriction-Modification Systems at the Single-Cell
and Population Level. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:th_916.
short: M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell
and Population Level, Institute of Science and Technology Austria, 2017.
corr_author: '1'
date_created: 2018-12-11T11:45:10Z
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status: public
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: Biology of restriction-modification systems at the single-cell and population
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
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...
---
_id: '561'
abstract:
- lang: eng
text: Restriction–modification systems are widespread genetic elements that protect
bacteria from bacteriophage infections by recognizing and cleaving heterologous
DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence
shows that restriction sites are significantly underrepresented in bacteriophage
genomes, presumably because bacteriophages with fewer restriction sites are more
likely to escape cleavage by restriction–modification systems. However, how mutations
in restriction sites affect the likelihood of bacteriophage escape is unknown.
Using the bacteriophage l and the restriction–modification system EcoRI, we show
that while mutation effects at different restriction sites are unequal, they are
independent. As a result, the probability of bacteriophage escape increases with
each mutated restriction site. Our results experimentally support the role of
restriction site avoidance as a response to selection imposed by restriction–modification
systems and offer an insight into the events underlying the process of bacteriophage
escape.
acknowledgement: This work was funded by an HFSP Young Investigators' grant RGY0079/2011
(C.C.G.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science
at the Institute of Science and Technology Austria.
article_number: '20170646'
article_processing_charge: No
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author:
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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: Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape
from restriction–modification. Biology Letters. 2017;13(12). doi:10.1098/rsbl.2017.0646
apa: Pleska, M., & Guet, C. C. (2017). Effects of mutations in phage restriction
sites during escape from restriction–modification. Biology Letters. The
Royal Society. https://doi.org/10.1098/rsbl.2017.0646
chicago: Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction
Sites during Escape from Restriction–Modification.” Biology Letters. The
Royal Society, 2017. https://doi.org/10.1098/rsbl.2017.0646.
ieee: M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites
during escape from restriction–modification,” Biology Letters, vol. 13,
no. 12. The Royal Society, 2017.
ista: Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during
escape from restriction–modification. Biology Letters. 13(12), 20170646.
mla: Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction
Sites during Escape from Restriction–Modification.” Biology Letters, vol.
13, no. 12, 20170646, The Royal Society, 2017, doi:10.1098/rsbl.2017.0646.
short: M. Pleska, C.C. Guet, Biology Letters 13 (2017).
corr_author: '1'
date_created: 2018-12-11T11:47:11Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2026-04-08T14:19:43Z
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oa: 1
oa_version: Published Version
pmid: 1
project:
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grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
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grant_number: '24210'
name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
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title: Effects of mutations in phage restriction sites during escape from restriction–modification
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 13
year: '2017'
...
---
_id: '1243'
abstract:
- lang: eng
text: Restriction-modification (RM) systems represent a minimal and ubiquitous biological
system of self/non-self discrimination in prokaryotes [1], which protects hosts
from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase
(M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by
methylating short specific DNA sequences called restriction sites, whereas R recognizes
unmethylated restriction sites as non-self and introduces a double-stranded DNA
break [3]. Restriction sites are significantly underrepresented in prokaryotic
genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally
leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore,
RM systems can promote DNA recombination [9] and contribute to genetic variation
in microbial populations, thus facilitating adaptive evolution [10]. However,
cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has
not been directly detected, and its cause, frequency, and outcome are unknown.
We quantify self-restriction caused by two RM systems of Escherichia coli and
find that, in agreement with levels of restriction site avoidance, EcoRI, but
not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic
process, which temporarily induces the SOS response, and is followed by DNA repair,
maintaining cell viability. We find that RM systems with higher restriction efficiency
against bacteriophage infections exhibit a higher rate of self-restriction, and
that this rate can be further increased by stochastic imbalance between R and
M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic
genomes.
acknowledgement: This work was funded by an HFSP Young Investigators’ grant. M.P.
is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute
of Science and Technology Austria. R.O. and Y.W. were supported by the Platform
for Dynamic Approaches to Living System from MEXT, Japan. We wish to thank I. Kobayashi
for providing us with the EcoRI and EcoRV plasmids, and A. Campbell for providing
us with the λ vir phage. We thank D. Siekhaus and C. Uhler and members of the C.C.G.
and J.P. Bollback laboratories for in-depth discussions. We thank B. Stern for comments
on an earlier version of the manuscript. We especially thank B.R. Levin for advice
and comments, and the anonymous reviewers for significantly improving the manuscript.
article_processing_charge: No
author:
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Long
full_name: Qian, Long
last_name: Qian
- first_name: Reiko
full_name: Okura, Reiko
last_name: Okura
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- first_name: Yuichi
full_name: Wakamoto, Yuichi
last_name: Wakamoto
- first_name: Edo
full_name: Kussell, Edo
last_name: Kussell
- 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: Pleska M, Qian L, Okura R, et al. Bacterial autoimmunity due to a restriction-modification
system. Current Biology. 2016;26(3):404-409. doi:10.1016/j.cub.2015.12.041
apa: Pleska, M., Qian, L., Okura, R., Bergmiller, T., Wakamoto, Y., Kussell, E.,
& Guet, C. C. (2016). Bacterial autoimmunity due to a restriction-modification
system. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2015.12.041
chicago: Pleska, Maros, Long Qian, Reiko Okura, Tobias Bergmiller, Yuichi Wakamoto,
Edo Kussell, and Calin C Guet. “Bacterial Autoimmunity Due to a Restriction-Modification
System.” Current Biology. Cell Press, 2016. https://doi.org/10.1016/j.cub.2015.12.041.
ieee: M. Pleska et al., “Bacterial autoimmunity due to a restriction-modification
system,” Current Biology, vol. 26, no. 3. Cell Press, pp. 404–409, 2016.
ista: Pleska M, Qian L, Okura R, Bergmiller T, Wakamoto Y, Kussell E, Guet CC. 2016.
Bacterial autoimmunity due to a restriction-modification system. Current Biology.
26(3), 404–409.
mla: Pleska, Maros, et al. “Bacterial Autoimmunity Due to a Restriction-Modification
System.” Current Biology, vol. 26, no. 3, Cell Press, 2016, pp. 404–09,
doi:10.1016/j.cub.2015.12.041.
short: M. Pleska, L. Qian, R. Okura, T. Bergmiller, Y. Wakamoto, E. Kussell, C.C.
Guet, Current Biology 26 (2016) 404–409.
date_created: 2018-12-11T11:50:54Z
date_published: 2016-02-08T00:00:00Z
date_updated: 2026-04-08T14:19:43Z
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grant_number: '24210'
name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
at the Single-Cell Level
publication: Current Biology
publication_status: published
publisher: Cell Press
publist_id: '6087'
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title: Bacterial autoimmunity due to a restriction-modification system
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...