An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis
Insertion sequences (IS) represent mobile genetic elements that have been shown to be associated with bacterial evolution and adaptation due to their effects on genome plasticity. In Bordetella pertussis, the causative agent of whooping cough, the numerous IS elements induce genomic rearrangements a...
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Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2451718 |
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| author | Alexandre D’Halluin Denisa Petráčková Ivana Čurnová Jakub Držmíšek Jan Čapek Peggy Bouquet Loïc Henin Rudy Antoine Loïc Coutte Camille Locht Branislav Večerek David Hot |
| author_facet | Alexandre D’Halluin Denisa Petráčková Ivana Čurnová Jakub Držmíšek Jan Čapek Peggy Bouquet Loïc Henin Rudy Antoine Loïc Coutte Camille Locht Branislav Večerek David Hot |
| author_sort | Alexandre D’Halluin |
| collection | DOAJ |
| description | Insertion sequences (IS) represent mobile genetic elements that have been shown to be associated with bacterial evolution and adaptation due to their effects on genome plasticity. In Bordetella pertussis, the causative agent of whooping cough, the numerous IS elements induce genomic rearrangements and contribute to the diversity of the global B. pertussis population. Previously, we have shown that the majority of IS-specific endogenous promoters induce the synthesis of alternative transcripts and thereby affect the transcriptional landscape of B. pertussis. Here, we describe the regulatory RNA Rfi2, which is transcribed from the Pout promoter of the IS481 gene BP1118 antisense to the adjacent fim2 gene encoding the major serotype 2 fimbrial subunit of B. pertussis. Among the classical bordetellae, Rfi2 is unique to B. pertussis, suggesting its specific role in virulence. We show that Rfi2 RNA attenuates fim2 transcription and, consequently, the production of the Fim2 protein. Interestingly, the mutant that does not produce Rfi2 displayed significantly increased cytotoxicity towards human macrophages compared to the parental strain. This observation suggests that the Rfi2-mediated reduction in cytotoxicity represents an evolutionary adaptation of B. pertussis that fine-tunes its interaction with the human host. Given the immunogenicity of Fim2, we further hypothesize that Rfi2-mediated modulation of Fim2 production contributes to immune evasion. To our knowledge, Rfi2 represents the first functionally characterized IS element-driven antisense RNA that modulates the expression of a virulence gene. |
| format | Article |
| id | doaj-art-70da6e624546457f917c3c0332bbe52a |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-70da6e624546457f917c3c0332bbe52a2025-01-27T13:44:24ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2451718An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussisAlexandre D’Halluin0Denisa Petráčková1Ivana Čurnová2Jakub Držmíšek3Jan Čapek4Peggy Bouquet5Loïc Henin6Rudy Antoine7Loïc Coutte8Camille Locht9Branislav Večerek10David Hot11U1019 – UMR8204 – CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institute Pasteur de Lille, Lille, FranceLaboratory of Post-Transcriptional Control of Gene Expression, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Post-Transcriptional Control of Gene Expression, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Post-Transcriptional Control of Gene Expression, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicLaboratory of Post-Transcriptional Control of Gene Expression, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicU1019 – UMR8204 – CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institute Pasteur de Lille, Lille, FranceU1019 – UMR8204 – CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institute Pasteur de Lille, Lille, FranceU1019 – UMR8204 – CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institute Pasteur de Lille, Lille, FranceU1019 – UMR8204 – CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institute Pasteur de Lille, Lille, FranceU1019 – UMR8204 – CIIL - Center for Infection and Immunity of Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institute Pasteur de Lille, Lille, FranceLaboratory of Post-Transcriptional Control of Gene Expression, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000, Lille, FranceInsertion sequences (IS) represent mobile genetic elements that have been shown to be associated with bacterial evolution and adaptation due to their effects on genome plasticity. In Bordetella pertussis, the causative agent of whooping cough, the numerous IS elements induce genomic rearrangements and contribute to the diversity of the global B. pertussis population. Previously, we have shown that the majority of IS-specific endogenous promoters induce the synthesis of alternative transcripts and thereby affect the transcriptional landscape of B. pertussis. Here, we describe the regulatory RNA Rfi2, which is transcribed from the Pout promoter of the IS481 gene BP1118 antisense to the adjacent fim2 gene encoding the major serotype 2 fimbrial subunit of B. pertussis. Among the classical bordetellae, Rfi2 is unique to B. pertussis, suggesting its specific role in virulence. We show that Rfi2 RNA attenuates fim2 transcription and, consequently, the production of the Fim2 protein. Interestingly, the mutant that does not produce Rfi2 displayed significantly increased cytotoxicity towards human macrophages compared to the parental strain. This observation suggests that the Rfi2-mediated reduction in cytotoxicity represents an evolutionary adaptation of B. pertussis that fine-tunes its interaction with the human host. Given the immunogenicity of Fim2, we further hypothesize that Rfi2-mediated modulation of Fim2 production contributes to immune evasion. To our knowledge, Rfi2 represents the first functionally characterized IS element-driven antisense RNA that modulates the expression of a virulence gene.https://www.tandfonline.com/doi/10.1080/22221751.2025.2451718Bordetella pertussisantisense RNAinsertion sequencefimbriae serotype 2modulation of virulencecytotoxicity towards macrophages |
| spellingShingle | Alexandre D’Halluin Denisa Petráčková Ivana Čurnová Jakub Držmíšek Jan Čapek Peggy Bouquet Loïc Henin Rudy Antoine Loïc Coutte Camille Locht Branislav Večerek David Hot An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis Emerging Microbes and Infections Bordetella pertussis antisense RNA insertion sequence fimbriae serotype 2 modulation of virulence cytotoxicity towards macrophages |
| title | An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis |
| title_full | An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis |
| title_fullStr | An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis |
| title_full_unstemmed | An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis |
| title_short | An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of Bordetella pertussis |
| title_sort | is element driven antisense rna attenuates the expression of serotype 2 fimbriae and the cytotoxicity of bordetella pertussis |
| topic | Bordetella pertussis antisense RNA insertion sequence fimbriae serotype 2 modulation of virulence cytotoxicity towards macrophages |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2025.2451718 |
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