T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis
Bordetella pertussis is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, B. pertussis produces the type III secretion system, but its role in the pathogenesis of B. pertussis is enigmatic and yet to...
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2272638 |
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| author | Jakub Držmíšek Denisa Petráčková Ana Dienstbier Ivana Čurnová Branislav Večerek |
| author_facet | Jakub Držmíšek Denisa Petráčková Ana Dienstbier Ivana Čurnová Branislav Večerek |
| author_sort | Jakub Držmíšek |
| collection | DOAJ |
| description | Bordetella pertussis is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, B. pertussis produces the type III secretion system, but its role in the pathogenesis of B. pertussis is enigmatic and yet to be elucidated. Here, we combined RNA-seq, LC-MS/MS, and co-immunoprecipitation techniques to identify and characterize the novel CesT family T3SS chaperone BP2265. We show that this chaperone specifically interacts with the secreted T3SS regulator BtrA and represents the first non-flagellar chaperone required for the secretion of an anti-sigma factor. In its absence, secretion but not production of BtrA and most T3SS substrates is severely impaired. It appears that the role of BtrA in regulating T3SS extends beyond its activity as an antagonist of the sigma factor BtrS. Predictions made by artificial intelligence system AlphaFold support the chaperone function of BP2265 towards BtrA and outline the structural basis for the interaction of BtrA with its target BtrS. We propose to rename BP2265 to BtcB for the Bordetella type III chaperone of BtrA.In addition, the absence of the BtcB chaperone results in increased expression of numerous flagellar genes and several virulence genes. While increased production of flagellar proteins and intimin BipA translated into increased biofilm formation by the mutant, enhanced production of virulence factors resulted in increased cytotoxicity towards human macrophages. We hypothesize that these phenotypic traits result indirectly from impaired secretion of BtrA and altered activity of the BtrA/BtrS regulatory node. |
| format | Article |
| id | doaj-art-768a7091d3594313b1ff7bd7e4f55dd8 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-768a7091d3594313b1ff7bd7e4f55dd82025-08-20T02:37:28ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2272638T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussisJakub Držmíšek0Denisa Petráčková1Ana Dienstbier2Ivana Čurnová3Branislav Večerek4Laboratory 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 RepublicLaboratory of post-transcriptional control of gene expression, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech RepublicBordetella pertussis is a Gram-negative, strictly human re-emerging respiratory pathogen and the causative agent of whooping cough. Similar to other Gram-negative pathogens, B. pertussis produces the type III secretion system, but its role in the pathogenesis of B. pertussis is enigmatic and yet to be elucidated. Here, we combined RNA-seq, LC-MS/MS, and co-immunoprecipitation techniques to identify and characterize the novel CesT family T3SS chaperone BP2265. We show that this chaperone specifically interacts with the secreted T3SS regulator BtrA and represents the first non-flagellar chaperone required for the secretion of an anti-sigma factor. In its absence, secretion but not production of BtrA and most T3SS substrates is severely impaired. It appears that the role of BtrA in regulating T3SS extends beyond its activity as an antagonist of the sigma factor BtrS. Predictions made by artificial intelligence system AlphaFold support the chaperone function of BP2265 towards BtrA and outline the structural basis for the interaction of BtrA with its target BtrS. We propose to rename BP2265 to BtcB for the Bordetella type III chaperone of BtrA.In addition, the absence of the BtcB chaperone results in increased expression of numerous flagellar genes and several virulence genes. While increased production of flagellar proteins and intimin BipA translated into increased biofilm formation by the mutant, enhanced production of virulence factors resulted in increased cytotoxicity towards human macrophages. We hypothesize that these phenotypic traits result indirectly from impaired secretion of BtrA and altered activity of the BtrA/BtrS regulatory node.https://www.tandfonline.com/doi/10.1080/22221751.2023.2272638Bordetella pertussisT3SSCesT chaperoneanti-sigma factorbiofilm |
| spellingShingle | Jakub Držmíšek Denisa Petráčková Ana Dienstbier Ivana Čurnová Branislav Večerek T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis Emerging Microbes and Infections Bordetella pertussis T3SS CesT chaperone anti-sigma factor biofilm |
| title | T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis |
| title_full | T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis |
| title_fullStr | T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis |
| title_full_unstemmed | T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis |
| title_short | T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis |
| title_sort | t3ss chaperone of the cest family is required for secretion of the anti sigma factor btra in bordetella pertussis |
| topic | Bordetella pertussis T3SS CesT chaperone anti-sigma factor biofilm |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2272638 |
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