The Type III Secreted Protein BspR Regulates the Virulence Genes in Bordetella bronchiseptica
Open Access
- 11 June 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (6), e38925
- https://doi.org/10.1371/journal.pone.0038925
Abstract
Bordetella bronchiseptica is closely related with B. pertussis and B. parapertussis, the causative agents of whooping cough. These pathogenic species share a number of virulence genes, including the gene locus for the type III secretion system (T3SS) that delivers effector proteins. To identify unknown type III effectors in Bordetella, secreted proteins in the bacterial culture supernatants of wild-type B. bronchiseptica and an isogenic T3SS-deficient mutant were compared with iTRAQ-based, quantitative proteomic analysis method. BB1639, annotated as a hypothetical protein, was identified as a novel type III secreted protein and was designated BspR (Bordetella secreted protein regulator). The virulence of a BspR mutant (ΔbspR) in B. bronchiseptica was significantly attenuated in a mouse infection model. BspR was also highly conserved in B. pertussis and B. parapertussis, suggesting that BspR is an essential virulence factor in these three Bordetella species. Interestingly, the BspR-deficient strain showed hyper-secretion of T3SS-related proteins. Furthermore, T3SS-dependent host cell cytotoxicity and hemolytic activity were also enhanced in the absence of BspR. By contrast, the expression of filamentous hemagglutinin, pertactin, and adenylate cyclase toxin was completely abolished in the BspR-deficient strain. Finally, we demonstrated that BspR is involved in the iron-responsive regulation of T3SS. Thus, Bordetella virulence factors are coordinately but inversely controlled by BspR, which functions as a regulator in response to iron starvation.Keywords
This publication has 47 references indexed in Scilit:
- Transcriptional Profiling of the Iron Starvation Response in Bordetella pertussis Provides New Insights into Siderophore Utilization and Virulence Gene ExpressionJournal of Bacteriology, 2011
- Bordetella evades the host immune system by inducing IL-10 through a type III effector, BopNThe Journal of Experimental Medicine, 2009
- Bordetella Bsp22 forms a filamentous type III secretion system tip complex and is immunoprotective in vitro and in vivoMolecular Microbiology, 2009
- Temporal signaling and differential expression of Bordetella iron transport systems: the role of ferrimones and positive regulatorsBioMetals, 2009
- MetaGeneAnnotator: Detecting Species-Specific Patterns of Ribosomal Binding Site for Precise Gene Prediction in Anonymous Prokaryotic and Phage GenomesDNA Research, 2008
- Regulation of bacterial RNA polymerase σ factor activity: a structural perspectiveCurrent Opinion in Microbiology, 2008
- Cross Talk between Type III Secretion and Flagellar Assembly Systems in Pseudomonas aeruginosaJournal of Bacteriology, 2007
- Functional specialization within the Fur family of metalloregulatorsBioMetals, 2007
- Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due toBordetella pertussisand OtherBordetellaSubspeciesClinical Microbiology Reviews, 2005
- THE ANTI-SIGMA FACTORSAnnual Review of Microbiology, 1998