{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:38:02Z","timestamp":1791088682992,"version":"4.1.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2024,4,16]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n The regulation of\n Bordetella pertussis<\/jats:italic>\n virulence is mediated by the two-component system BvgA\/S, which activates the transcription of virulence-activated genes (\n vag<\/jats:italic>\n s). In the avirulent phase, the\n vag<\/jats:italic>\n s are not expressed, but instead, virulence-repressed genes (\n vrg<\/jats:italic>\n s) are expressed, under the control of another two-component system, RisA\/K. Here, we combined transcriptomic and chromatin immunoprecipitation sequencing (ChIPseq) data to examine the RisA\/K regulon. We performed RNAseq analyses of RisA-deficient and RisA-phosphoablative\n B. pertussis<\/jats:italic>\n mutants cultivated in virulent and avirulent conditions. We confirmed that the expression of most\n vrg<\/jats:italic>\n s is regulated by phosphorylated RisA. However, the expression of some, including those involved in flagellum biosynthesis and chemotaxis, requires RisA independently of phosphorylation. Many RisA-regulated genes encode proteins with regulatory functions, suggesting multiple RisA regulation cascades. By ChIPseq analyses, we identified 430 RisA-binding sites, 208 within promoter regions, 201 within open reading frames, and 21 in non-coding regions. RisA binding was demonstrated in the promoter regions of most\n vrg<\/jats:italic>\n s and, surprisingly, of some\n vag<\/jats:italic>\n s, as well as for other genes not identified as\n vag<\/jats:italic>\n s or\n vrg<\/jats:italic>\n s. Unexpectedly, many genes, including some\n vag<\/jats:italic>\n s, like\n prn<\/jats:italic>\n ,\n brpL<\/jats:italic>\n ,\n bipA,<\/jats:italic>\n and\n cyaA<\/jats:italic>\n , contain a BvgA-binding site and a RisA-binding site, which increases the complexity of the RisAK\/BvgAS network in\n B. pertussis<\/jats:italic>\n virulence regulation.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n The expression of virulence-activated genes (\n vag<\/jats:italic>\n s) of\n Bordetella pertussis<\/jats:italic>\n , the etiological agent of whooping cough, is under the transcriptional control of the two-component system BvgA\/S, which allows the bacterium to switch between virulent and avirulent phases. In addition, the more recently identified two-component system RisA\/K is required for the expression of\n B. pertussis<\/jats:italic>\n genes, collectively named\n vrg<\/jats:italic>\n s, that are repressed during the virulent phase but activated during the avirulent phase. We have characterized the RisA\/K regulon by combined transcriptomic and chromatin immunoprecipitation sequencing analyses. We identified more than 400 RisA-binding sites. Many of them are localized in promoter regions, especially\n vrg<\/jats:italic>\n s, but some were found within open reading frames and in non-coding regions. Surprisingly, RisA-binding sites were also found in promoter regions of some\n vag<\/jats:italic>\n s, illustrating the previously underappreciated complexity of virulence regulation in\n B. pertussis<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/msystems.00951-23","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:01:32Z","timestamp":1710244892000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Combined transcriptomic and ChIPseq analyses of the\n Bordetella pertussis<\/i>\n RisA regulon"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8626-8109","authenticated-orcid":true,"given":"Lo\u00efc","family":"Coutte","sequence":"first","affiliation":[{"name":"U1019\u2013UMR9017, University of Lille, CNRS, Inserm, CHU Lille, CIIL-Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy","family":"Antoine","sequence":"additional","affiliation":[{"name":"U1019\u2013UMR9017, University of Lille, CNRS, Inserm, CHU Lille, CIIL-Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Slupek","sequence":"additional","affiliation":[{"name":"U1019\u2013UMR9017, University of Lille, CNRS, Inserm, CHU Lille, CIIL-Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Locht","sequence":"additional","affiliation":[{"name":"U1019\u2013UMR9017, University of Lille, CNRS, Inserm, CHU Lille, CIIL-Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2019.01.002"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00208-20"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004700"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/s0022172400038134"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep32774"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00475-17"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.7.1682-1690.1998"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftv068"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.3.769-778.1994"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00175-18"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.17.5234-5241.1999"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01526-17"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0010045"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2018.1462655"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.067306.118"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-254"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn339"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05781.x"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2012_257"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02535-22"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176396"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04526.x"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.5.1648-1658.2005"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(86)90318-5"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1183-784"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt444"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004183"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"}],"container-title":["mSystems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.00951-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.00951-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T15:48:11Z","timestamp":1713282491000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msystems.00951-23"}},"subtitle":[],"editor":[{"given":"Mark J.","family":"Mandel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,16]]}},"alternative-id":["10.1128\/msystems.00951-23"],"URL":"https:\/\/doi.org\/10.1128\/msystems.00951-23","relation":{},"ISSN":["2379-5077"],"issn-type":[{"value":"2379-5077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]},"assertion":[{"value":"2023-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00951-23"}}