--- _id: '423' abstract: - lang: eng text: Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity. acknowledgement: "We are grateful to Remy Chait for his help and assistance with establishing our experimental setups and to Tobias Bergmiller for valuable insights into some specific experimental details. We thank Luciano Marraffini for donating us the pCas9 plasmid used in this study. We also want to express our gratitude to Seth Barribeau, Andrea Betancourt, Călin Guet, Mato Lagator, Tiago Paixão and Maroš Pleška for valuable discussions on the manuscript. Finally, we would like to thank the \r\neditors and reviewers for their helpful comments and suggestions." article_number: e32035 article_processing_charge: No author: - first_name: Pavel full_name: Payne, Pavel id: 35F78294-F248-11E8-B48F-1D18A9856A87 last_name: Payne orcid: 0000-0002-2711-9453 - first_name: Lukas full_name: Geyrhofer, Lukas last_name: Geyrhofer - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: Payne P, Geyrhofer L, Barton NH, Bollback JP. CRISPR-based herd immunity can limit phage epidemics in bacterial populations. eLife. 2018;7. doi:10.7554/eLife.32035 apa: Payne, P., Geyrhofer, L., Barton, N. H., & Bollback, J. P. (2018). CRISPR-based herd immunity can limit phage epidemics in bacterial populations. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.32035 chicago: Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback. “CRISPR-Based Herd Immunity Can Limit Phage Epidemics in Bacterial Populations.” ELife. eLife Sciences Publications, 2018. https://doi.org/10.7554/eLife.32035. ieee: P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “CRISPR-based herd immunity can limit phage epidemics in bacterial populations,” eLife, vol. 7. eLife Sciences Publications, 2018. ista: Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. CRISPR-based herd immunity can limit phage epidemics in bacterial populations. eLife. 7, e32035. mla: Payne, Pavel, et al. “CRISPR-Based Herd Immunity Can Limit Phage Epidemics in Bacterial Populations.” ELife, vol. 7, e32035, eLife Sciences Publications, 2018, doi:10.7554/eLife.32035. short: P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, ELife 7 (2018). date_created: 2018-12-11T11:46:23Z date_published: 2018-03-09T00:00:00Z date_updated: 2023-09-11T12:49:17Z day: '09' ddc: - '576' department: - _id: NiBa - _id: JoBo doi: 10.7554/eLife.32035 ec_funded: 1 external_id: isi: - '000431035800001' file: - access_level: open_access checksum: 447cf6e680bdc3c01062a8737d876569 content_type: application/pdf creator: dernst date_created: 2018-12-17T10:36:07Z date_updated: 2020-07-14T12:46:25Z file_id: '5689' file_name: 2018_eLife_Payne.pdf file_size: 3533881 relation: main_file file_date_updated: 2020-07-14T12:46:25Z has_accepted_license: '1' intvolume: ' 7' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version project: - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer publication: eLife publication_status: published publisher: eLife Sciences Publications publist_id: '7400' quality_controlled: '1' related_material: record: - id: '9840' relation: research_data status: public scopus_import: '1' status: public title: CRISPR-based herd immunity can limit phage epidemics in bacterial populations 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: 7 year: '2018' ... --- _id: '9840' abstract: - lang: eng text: Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity. article_processing_charge: No author: - first_name: Pavel full_name: Payne, Pavel id: 35F78294-F248-11E8-B48F-1D18A9856A87 last_name: Payne orcid: 0000-0002-2711-9453 - first_name: Lukas full_name: Geyrhofer, Lukas last_name: Geyrhofer - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: 'Payne P, Geyrhofer L, Barton NH, Bollback JP. Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations. 2018. doi:10.5061/dryad.42n44' apa: 'Payne, P., Geyrhofer, L., Barton, N. H., & Bollback, J. P. (2018). Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations. Dryad. https://doi.org/10.5061/dryad.42n44' chicago: 'Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback. “Data from: CRISPR-Based Herd Immunity Limits Phage Epidemics in Bacterial Populations.” Dryad, 2018. https://doi.org/10.5061/dryad.42n44.' ieee: 'P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations.” Dryad, 2018.' ista: 'Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations, Dryad, 10.5061/dryad.42n44.' mla: 'Payne, Pavel, et al. Data from: CRISPR-Based Herd Immunity Limits Phage Epidemics in Bacterial Populations. Dryad, 2018, doi:10.5061/dryad.42n44.' short: P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, (2018). date_created: 2021-08-09T13:10:02Z date_published: 2018-03-12T00:00:00Z date_updated: 2023-09-11T12:49:17Z day: '12' department: - _id: NiBa - _id: JoBo doi: 10.5061/dryad.42n44 main_file_link: - open_access: '1' url: https://doi.org/10.5061/dryad.42n44 month: '03' oa: 1 oa_version: Published Version publisher: Dryad related_material: record: - id: '423' relation: used_in_publication status: public status: public title: 'Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations' type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2018' ... --- _id: '67' abstract: - lang: eng text: 'Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.' article_processing_charge: No article_type: original author: - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 - 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 citation: ama: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2018;2(10):1633-1643. doi:10.1038/s41559-018-0651-y apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. Nature Publishing Group. https://doi.org/10.1038/s41559-018-0651-y chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution. Nature Publishing Group, 2018. https://doi.org/10.1038/s41559-018-0651-y. ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” Nature Ecology and Evolution, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018. ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643. mla: Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:10.1038/s41559-018-0651-y. short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643. date_created: 2018-12-11T11:44:27Z date_published: 2018-09-10T00:00:00Z date_updated: 2024-03-27T23:30:48Z day: '10' ddc: - '570' department: - _id: CaGu - _id: GaTk - _id: JoBo doi: 10.1038/s41559-018-0651-y ec_funded: 1 external_id: isi: - '000447947600021' file: - access_level: open_access checksum: 383a2e2c944a856e2e821ec8e7bf71b6 content_type: application/pdf creator: dernst date_created: 2020-05-14T11:28:52Z date_updated: 2020-07-14T12:47:37Z file_id: '7830' file_name: 2018_NatureEcology_Igler.pdf file_size: 1135973 relation: main_file file_date_updated: 2020-07-14T12:47:37Z has_accepted_license: '1' intvolume: ' 2' isi: 1 issue: '10' language: - iso: eng month: '09' oa: 1 oa_version: Submitted Version page: 1633 - 1643 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer - _id: 251EE76E-B435-11E9-9278-68D0E5697425 grant_number: '24573' name: Design principles underlying genetic switch architecture (DOC Fellowship) publication: Nature Ecology and Evolution publication_status: published publisher: Nature Publishing Group publist_id: '7987' quality_controlled: '1' related_material: record: - id: '5585' relation: popular_science status: public - id: '6371' relation: dissertation_contains status: public scopus_import: '1' status: public title: Evolutionary potential of transcription factors for gene regulatory rewiring type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 2 year: '2018' ... --- _id: '570' abstract: - lang: eng text: 'Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution. ' article_number: e28921 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: Hande full_name: Acar, Hande id: 2DDF136A-F248-11E8-B48F-1D18A9856A87 last_name: Acar orcid: 0000-0003-1986-9753 - 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 citation: ama: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921 apa: Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921 chicago: Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921. ieee: M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921. mla: Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications, 2017, doi:10.7554/eLife.28921. short: M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017). date_created: 2018-12-11T11:47:14Z date_published: 2017-11-13T00:00:00Z date_updated: 2021-01-12T08:03:15Z day: '13' ddc: - '576' department: - _id: CaGu - _id: JoBo - _id: NiBa doi: 10.7554/eLife.28921 ec_funded: 1 file: - access_level: open_access checksum: 273ab17f33305e4eaafd911ff88e7c5b content_type: application/pdf creator: system date_created: 2018-12-12T10:14:42Z date_updated: 2020-07-14T12:47:10Z file_id: '5096' file_name: IST-2017-918-v1+1_elife-28921-figures-v3.pdf file_size: 8453470 relation: main_file - access_level: open_access checksum: b433f90576c7be597cd43367946f8e7f content_type: application/pdf creator: system date_created: 2018-12-12T10:14:43Z date_updated: 2020-07-14T12:47:10Z file_id: '5097' file_name: IST-2017-918-v1+2_elife-28921-v3.pdf file_size: 1953221 relation: main_file file_date_updated: 2020-07-14T12:47:10Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng month: '11' oa: 1 oa_version: Published Version project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '7244' pubrep_id: '918' quality_controlled: '1' scopus_import: 1 status: public title: Regulatory network structure determines patterns of intermolecular epistasis 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: 6 year: '2017' ... --- _id: '6291' abstract: - lang: eng text: Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Pavel full_name: Payne, Pavel id: 35F78294-F248-11E8-B48F-1D18A9856A87 last_name: Payne orcid: 0000-0002-2711-9453 citation: ama: Payne P. Bacterial herd and social immunity to phages. 2017. apa: Payne, P. (2017). Bacterial herd and social immunity to phages. Institute of Science and Technology Austria. chicago: Payne, Pavel. “Bacterial Herd and Social Immunity to Phages.” Institute of Science and Technology Austria, 2017. ieee: P. Payne, “Bacterial herd and social immunity to phages,” Institute of Science and Technology Austria, 2017. ista: Payne P. 2017. Bacterial herd and social immunity to phages. Institute of Science and Technology Austria. mla: Payne, Pavel. Bacterial Herd and Social Immunity to Phages. Institute of Science and Technology Austria, 2017. short: P. Payne, Bacterial Herd and Social Immunity to Phages, Institute of Science and Technology Austria, 2017. date_created: 2019-04-09T15:16:45Z date_published: 2017-02-01T00:00:00Z date_updated: 2023-09-07T12:00:00Z day: '01' ddc: - '570' degree_awarded: PhD department: - _id: NiBa - _id: JoBo file: - access_level: closed checksum: a0fc5c26a89c0ea759947ffba87d0d8f content_type: application/pdf creator: dernst date_created: 2019-04-09T15:15:32Z date_updated: 2020-07-14T12:47:27Z file_id: '6292' file_name: thesis_pavel_payne_final_w_signature_page.pdf file_size: 3025175 relation: main_file - access_level: open_access checksum: af531e921a7f64a9e0af4cd8783b2226 content_type: application/pdf creator: dernst date_created: 2021-02-22T13:45:59Z date_updated: 2021-02-22T13:45:59Z file_id: '9187' file_name: 2017_Payne_Thesis.pdf file_size: 3111536 relation: main_file success: 1 file_date_updated: 2021-02-22T13:45:59Z has_accepted_license: '1' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: '83' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - 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: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 title: Bacterial herd and social immunity to phages type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2017' ...