[{"ddc":["570"],"related_material":{"record":[{"status":"public","relation":"research_data","id":"9786"}]},"article_number":"e1007168","isi":1,"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)"},"external_id":{"isi":["000481577700032"]},"title":"Molecular noise of innate immunity shapes bacteria-phage ecologies","doi":"10.1371/journal.pcbi.1007168","year":"2019","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","quality_controlled":"1","project":[{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","grant_number":"24210"},{"grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems"}],"_id":"6784","publication_identifier":{"eissn":["1553-7358"]},"volume":15,"oa":1,"date_updated":"2023-08-29T07:10:06Z","article_processing_charge":"No","author":[{"first_name":"Jakob","orcid":"0000-0003-1615-3282","last_name":"Ruess","full_name":"Ruess, Jakob","id":"4A245D00-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Maros","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"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.","lang":"eng"}],"publication_status":"published","citation":{"short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (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.","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes bacteria-phage ecologies. <i>PLoS Computational Biology</i>. 2019;15(7). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">10.1371/journal.pcbi.1007168</a>","mla":"Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” <i>PLoS Computational Biology</i>, vol. 15, no. 7, e1007168, Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">10.1371/journal.pcbi.1007168</a>.","chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” <i>PLoS Computational Biology</i>. Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">https://doi.org/10.1371/journal.pcbi.1007168</a>.","apa":"Ruess, J., Pleska, M., Guet, C. C., &#38; Tkačik, G. (2019). Molecular noise of innate immunity shapes bacteria-phage ecologies. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">https://doi.org/10.1371/journal.pcbi.1007168</a>","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate immunity shapes bacteria-phage ecologies,” <i>PLoS Computational Biology</i>, vol. 15, no. 7. Public Library of Science, 2019."},"file":[{"date_updated":"2020-07-14T12:47:40Z","access_level":"open_access","file_name":"2019_PlosComputBiology_Ruess.pdf","file_size":2200003,"date_created":"2019-08-12T12:27:26Z","checksum":"7ded4721b41c2a0fc66a1c634540416a","content_type":"application/pdf","relation":"main_file","file_id":"6803","creator":"dernst"}],"date_created":"2019-08-11T21:59:19Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"publisher":"Public Library of Science","scopus_import":"1","article_type":"original","date_published":"2019-07-02T00:00:00Z","month":"07","file_date_updated":"2020-07-14T12:47:40Z","issue":"7","publication":"PLoS Computational Biology","status":"public","intvolume":"        15","type":"journal_article","day":"02"},{"issue":"2","publication":"Nature Ecology and Evolution","page":"359 - 366","intvolume":"         2","status":"public","day":"01","type":"journal_article","date_created":"2018-12-11T11:46:35Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Springer Nature","scopus_import":"1","language":[{"iso":"eng"}],"month":"02","date_published":"2018-02-01T00:00:00Z","_id":"457","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","quality_controlled":"1","oa_version":"None","project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"},{"grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant)"},{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","grant_number":"24210"}],"volume":2,"date_updated":"2023-09-15T12:04:57Z","publist_id":"7364","article_processing_charge":"No","abstract":[{"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","lang":"eng"}],"author":[{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros","last_name":"Pleska"},{"first_name":"Moritz","last_name":"Lang","full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Refardt","full_name":"Refardt, Dominik","first_name":"Dominik"},{"first_name":"Bruce","full_name":"Levin, Bruce","last_name":"Levin"},{"full_name":"Guet, Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","citation":{"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.","short":"M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution 2 (2018) 359–366.","ama":"Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. <i>Nature Ecology and Evolution</i>. 2018;2(2):359-366. doi:<a href=\"https://doi.org/10.1038/s41559-017-0424-z\">10.1038/s41559-017-0424-z</a>","mla":"Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” <i>Nature Ecology and Evolution</i>, vol. 2, no. 2, Springer Nature, 2018, pp. 359–66, doi:<a href=\"https://doi.org/10.1038/s41559-017-0424-z\">10.1038/s41559-017-0424-z</a>.","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.” <i>Nature Ecology and Evolution</i>. Springer Nature, 2018. <a href=\"https://doi.org/10.1038/s41559-017-0424-z\">https://doi.org/10.1038/s41559-017-0424-z</a>.","apa":"Pleska, M., Lang, M., Refardt, D., Levin, B., &#38; Guet, C. C. (2018). Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. <i>Nature Ecology and Evolution</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41559-017-0424-z\">https://doi.org/10.1038/s41559-017-0424-z</a>","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,” <i>Nature Ecology and Evolution</i>, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018."},"related_material":{"record":[{"id":"202","relation":"dissertation_contains","status":"public"}]},"isi":1,"title":"Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity","external_id":{"isi":["000426516400027"]},"doi":"10.1038/s41559-017-0424-z","year":"2018","ec_funded":1},{"month":"12","article_type":"original","date_published":"2017-12-01T00:00:00Z","scopus_import":"1","publisher":"The Royal Society","language":[{"iso":"eng"}],"department":[{"_id":"CaGu"}],"date_created":"2018-12-11T11:47:11Z","day":"01","type":"journal_article","intvolume":"        13","status":"public","publication":"Biology Letters","issue":"12","doi":"10.1098/rsbl.2017.0646","year":"2017","title":"Effects of mutations in phage restriction sites during escape from restriction–modification","external_id":{"pmid":["29237814"]},"article_number":"20170646","main_file_link":[{"url":"https://doi.org/10.1098/rsbl.2017.0646","open_access":"1"}],"related_material":{"record":[{"relation":"research_data","id":"9847","status":"public"},{"status":"public","relation":"dissertation_contains","id":"202"}]},"citation":{"apa":"Pleska, M., &#38; Guet, C. C. (2017). Effects of mutations in phage restriction sites during escape from restriction–modification. <i>Biology Letters</i>. The Royal Society. <a href=\"https://doi.org/10.1098/rsbl.2017.0646\">https://doi.org/10.1098/rsbl.2017.0646</a>","ieee":"M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites during escape from restriction–modification,” <i>Biology Letters</i>, vol. 13, no. 12. The Royal Society, 2017.","chicago":"Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>. The Royal Society, 2017. <a href=\"https://doi.org/10.1098/rsbl.2017.0646\">https://doi.org/10.1098/rsbl.2017.0646</a>.","mla":"Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>, vol. 13, no. 12, 20170646, The Royal Society, 2017, doi:<a href=\"https://doi.org/10.1098/rsbl.2017.0646\">10.1098/rsbl.2017.0646</a>.","ama":"Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape from restriction–modification. <i>Biology Letters</i>. 2017;13(12). doi:<a href=\"https://doi.org/10.1098/rsbl.2017.0646\">10.1098/rsbl.2017.0646</a>","short":"M. Pleska, C.C. Guet, Biology Letters 13 (2017).","ista":"Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646."},"publication_status":"published","abstract":[{"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.","lang":"eng"}],"author":[{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros","last_name":"Pleska"},{"first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","date_updated":"2023-09-07T11:59:32Z","volume":13,"oa":1,"publist_id":"7253","publication_identifier":{"issn":["1744-9561"]},"_id":"561","pmid":1,"oa_version":"Published Version","quality_controlled":"1","project":[{"name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant)","_id":"251BCBEC-B435-11E9-9278-68D0E5697425","grant_number":"RGY0079/2011"},{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","grant_number":"24210"}],"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.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"}]