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BtcB (BP2265) is a T3SS chaperone of the CesT family in Bordetella pertussis

ABSTRACT: Bordetella pertussis is a Gram-negative, strictly human respiratory pathogen and the causative agent of whooping cough (pertussis). Similar to other Gram-negative pathogens, B. pertussis produces a functional type III secretion system, but its role in pathogenesis of B. pertussis is enigmatic and has not yet been elucidated. Here, we applied omics RNA-seq as well as LC-MS/MS techniques and co-immunoprecipitation method to identify and characterize the novel CesT family T3SS chaperone BP2265. Our results show that the chaperone BP2265 specifically interacts with the secreted T3SS anti-sigma factor BtrA. Moreover, in the absence of the chaperone, secretion but not production of BtrA and several early, intermediate, and late T3SS substrates is severely impaired. It appears that the role of BtrA in regulating T3SS is more complex and extends beyond its activity as an antagonist of the sigma factor BtrS. We propose to rename BP2265 as BtcB for the Bordetella type III chaperone of BtrA.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Bordetella Pertussis B1917 Bordetella Pertussis (strain Tohama I / Atcc Baa-589 / Nctc 13251)

SUBMITTER: Denisa Petrackova

LAB HEAD: Branislav Vecerek, PhD

PROVIDER: PXD044487 | Pride | 2024-01-26

REPOSITORIES: Pride

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T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in Bordetella pertussis.

Držmíšek Jakub J Petráčková Denisa D Dienstbier Ana A Čurnová Ivana I Večerek Branislav B

Emerging microbes & infections 20231101 2

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 th ...[more]

PMID: 37850324

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Project description:Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx) production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR). The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn) and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by identifying novel vaccine candidates.

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Dataset Information

BtcB (BP2265) is a T3SS chaperone of the CesT family in Bordetella pertussis

Dataset's files

Publications

T3SS chaperone of the CesT family is required for secretion of the anti-sigma factor BtrA in <i>Bordetella pertussis</i>.

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