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Despite this, the pneumococcus makes up part of the commensal nasopharyngeal flora. How the pneumococcus switches from this commensal to pathogenic state and causes disease is unclear and very likely involves variability in expression of its virulence factors. Here, we used synthetic biology approaches to generate complex gene-regulatory networks such as logic gates and toggle switches. We show that these networks are functional in vivo to control capsule production in an influenza-superinfection model. This opens the field of systematically testing the role of phenotypic variation in pneumococcal virulence. The approaches used here may serve as an example for synthetic biology projects in unrelated organisms.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1920015117","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T20:15:32Z","timestamp":1603311332000},"page":"27608-27619","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":40,"title":["Synthetic gene-regulatory networks in the opportunistic human pathogen\n                    <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1073","volume":"117","author":[{"given":"Robin A.","family":"Sorg","sequence":"first","affiliation":[{"name":"Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, 9747 AG, Groningen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-8928","authenticated-orcid":false,"given":"Clement","family":"Gallay","sequence":"additional","affiliation":[{"name":"Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurye","family":"Van Maele","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille, CNRS, Inserm, Centre Hospitalier Universitaire de Lille, Institut Pasteur Lille, U1019\u2013UMR 9017\u2013CIIL\u2013Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-4652","authenticated-orcid":false,"given":"Jean-Claude","family":"Sirard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lille, CNRS, Inserm, Centre Hospitalier Universitaire de Lille, Institut Pasteur Lille, U1019\u2013UMR 9017\u2013CIIL\u2013Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3162-6634","authenticated-orcid":false,"given":"Jan-Willem","family":"Veening","sequence":"additional","affiliation":[{"name":"Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60733-4"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60222-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1871"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0001-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.21.6192-6202.2000"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002788"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1377"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601661200"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46423-0"},{"key":"e_1_3_4_10_2","first-page":"9971","article-title":"Deep genome annotation of the opportunistic human pathogen Streptococcus pneumoniae D39","volume":"46","author":"Slager J.","year":"2018","unstructured":"J. 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