--- _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: 2023-08-29T07:10:06Z 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 license: https://creativecommons.org/licenses/by/4.0/ 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: '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. date_created: 2018-12-11T11:46:35Z date_published: 2018-02-01T00:00:00Z date_updated: 2023-09-15T12:04:57Z day: '01' department: - _id: CaGu - _id: GaTk doi: 10.1038/s41559-017-0424-z ec_funded: 1 external_id: isi: - '000426516400027' intvolume: ' 2' isi: 1 issue: '2' language: - iso: eng 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 Systems (HFSP Young investigators' grant) - _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 (DOC Fellowship) publication: Nature Ecology and Evolution publication_status: published publisher: Springer Nature publist_id: '7364' quality_controlled: '1' related_material: record: - id: '202' relation: dissertation_contains status: public scopus_import: '1' status: public title: Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 2 year: '2018' ... --- _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 article_type: original 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). date_created: 2018-12-11T11:47:11Z date_published: 2017-12-01T00:00:00Z date_updated: 2023-09-07T11:59:32Z day: '01' department: - _id: CaGu doi: 10.1098/rsbl.2017.0646 external_id: pmid: - '29237814' intvolume: ' 13' issue: '12' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1098/rsbl.2017.0646 month: '12' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 251BCBEC-B435-11E9-9278-68D0E5697425 grant_number: RGY0079/2011 name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant) - _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 (DOC Fellowship) publication: Biology Letters publication_identifier: issn: - 1744-9561 publication_status: published publisher: The Royal Society publist_id: '7253' quality_controlled: '1' related_material: record: - id: '9847' relation: research_data status: public - id: '202' relation: dissertation_contains status: public scopus_import: '1' status: public title: Effects of mutations in phage restriction sites during escape from restriction–modification type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2017' ...