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FEMS Microbiology Reviews May 2011Pertussis, or whooping cough, is a highly contagious, acute respiratory disease of humans that is caused by the Gram-negative bacterial pathogen Bordetella pertussis. In... (Review)
Review
Pertussis, or whooping cough, is a highly contagious, acute respiratory disease of humans that is caused by the Gram-negative bacterial pathogen Bordetella pertussis. In the face of extensive global vaccination, this extremely monomorphic pathogen has persisted and re-emerged, causing approximately 300,000 deaths each year. In this review, we discuss the interaction of B. pertussis with the host mucosal epithelium and immune system. Using a large number of virulence factors, B. pertussis is able to create a niche for colonization in the human respiratory tract. The successful persistence of this pathogen is mainly due to its ability to interfere with almost every aspect of the immune system, from the inhibition of complement- and phagocyte-mediated killing to the suppression of T- and B-cell responses. Based on these insights, we delineate ideas for the rational design of improved vaccines that can target the 'weak spots' in the pathogenesis of this highly successful pathogen.
Topics: Animals; Bordetella pertussis; Humans; Mice; Virulence Factors; Whooping Cough
PubMed: 21204863
DOI: 10.1111/j.1574-6976.2010.00257.x -
Journal of Cystic Fibrosis : Official... Sep 2011Despite vaccination, pertussis is still endemic in the Netherlands. A literature search was performed to verify what is known about the role of Bordetella species in... (Review)
Review
Despite vaccination, pertussis is still endemic in the Netherlands. A literature search was performed to verify what is known about the role of Bordetella species in children with cystic fibrosis, with regard to the incidence of Bordetella infections, the involvement in pulmonary exacerbations and the influence on chronic course. Little is known about the frequency of Bordetella infections and the involvement of Bordetella species both in relation to the chronic course of cystic fibrosis and to pulmonary exacerbations. Since it is difficult to detect Bordetella species in cultures and few sputum cultures investigated have been obtained during an exacerbation, it is likely that the frequency of Bordetella species in CF patients is underestimated. Identification of Bordetella species in these patients may have serious consequences for the treatment of exacerbations in CF. Future research investigating the role of Bordetella species in cystic fibrosis should use specific techniques to detect Bordetella in cultures.
Topics: Acute Disease; Bordetella; Bordetella Infections; Child; Chronic Disease; Cystic Fibrosis; Humans; Incidence; Whooping Cough
PubMed: 21719361
DOI: 10.1016/j.jcf.2011.06.003 -
Molecular Microbiology Feb 2017Nicotinamide adenine dinucleotide (NAD) is produced via de novo biosynthesis pathways and by salvage or recycling routes. The classical Bordetella bacterial species are...
Nicotinamide adenine dinucleotide (NAD) is produced via de novo biosynthesis pathways and by salvage or recycling routes. The classical Bordetella bacterial species are known to be auxotrophic for nicotinamide or nicotinic acid. This study confirmed that Bordetella bronchiseptica, Bordetella pertussis and Bordetella parapertussis have the recycling/salvage pathway genes pncA and pncB, for use of nicotinamide or nicotinic acid, respectively, for NAD synthesis. Although these Bordetellae lack the nadA and nadB genes needed for de novo NAD biosynthesis, remarkably, they have one de novo pathway gene, nadC, encoding quinolinate phosphoribosyltransferase. Genomic analyses of taxonomically related Bordetella and Achromobacter species also indicated the presence of an 'orphan' nadC and the absence of nadA and nadB. When supplied as the sole NAD precursor, quinolinate promoted B. bronchiseptica growth, and the ability to use it required nadC. Co-expression of Bordetella nadC with the nadB and nadA genes of Paraburkholderia phytofirmans allowed B. bronchiseptica to grow in the absence of supplied pyridines, indicative of de novo NAD synthesis and functional confirmation of Bordetella NadC activity. Expression of nadC in B. bronchiseptica was influenced by nicotinic acid and by a NadQ family transcriptional repressor, indicating that these organisms prioritize their use of pyridines for NAD biosynthesis.
Topics: Bacterial Proteins; Biosynthetic Pathways; Bordetella; Genes, Bacterial; Mutation; NAD; Pentosyltransferases; Quinolinic Acid
PubMed: 27783449
DOI: 10.1111/mmi.13566 -
Microbiology (Reading, England) Sep 1994Three groups of monoclonal antibodies (mAbs) were produced that would be useful for immunochemical typing and diagnosis of infections due to Bordetella species, and for... (Comparative Study)
Comparative Study
Three groups of monoclonal antibodies (mAbs) were produced that would be useful for immunochemical typing and diagnosis of infections due to Bordetella species, and for the structural analysis of their lipopolysaccharides. PP6, a representative of the first group, recognizes an epitope shared by smooth-type Bordetella parapertussis and Bordetella bronchiseptica lipopolysaccharides (LPS). This epitope is carried by structurally identical polymeric O-chains (POC) present on both LPS molecules. PP8 and PP9 are representatives of the second group of mAbs. The interaction of PP8 and PP9 with B. parapertussis and B. bronchiseptica LPS requires POC, but periodate-sensitive sugar units of the core are also involved in the binding. The mAb BRg1 belongs to the third group, and specifically recognizes B. bronchiseptica LPS. Binding and inhibition studies with various Bordetella LPS molecules, and with their polysaccharide fragments, indicated that BRg1 interacts with a structure located at the hinge between the POC and a core region of the B. bronchiseptica LPS containing periodate-resistant sugars. This suggests that the structures of the hinge regions of the B. parapertussis and B. bronchiseptica LPS are different.
Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Antigens, Bacterial; Bordetella; Bordetella bronchiseptica; Cross Reactions; Epitopes; Hybridomas; Lipopolysaccharides; Mice; Species Specificity
PubMed: 7524956
DOI: 10.1099/13500872-140-9-2459 -
MBio Oct 2017Nearly all virulence factors in are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is...
Nearly all virulence factors in are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P), and virulence-activated genes (s) are expressed [Bvg(+) mode]. When BvgS is inactive and BvgA is not phosphorylated, virulence-repressed genes (s) are induced [Bvg(-) mode]. Here, we have used transcriptome sequencing (RNA-seq) and reverse transcription-quantitative PCR (RT-qPCR) to define the BvgAS-dependent regulon of Tohama I. Our analyses reveal more than 550 BvgA-regulated genes, of which 353 are newly identified. BvgA-activated genes include those encoding two-component systems (such as ), multiple other transcriptional regulators, and the extracytoplasmic function (ECF) sigma factor , which is needed for type 3 secretion system (T3SS) expression, further establishing the importance of BvgA~P as an apex regulator of transcriptional networks promoting virulence. Using transcription, we demonstrate that the promoter for is directly activated by BvgA~P. BvgA-FeBABE cleavage reactions identify BvgA~P binding sites centered at positions -41.5 and -63.5 in Most importantly, we show for the first time that genes for multiple and varied metabolic pathways are significantly upregulated in the Bvg(-) mode. These include genes for fatty acid and lipid metabolism, sugar and amino acid transporters, pyruvate dehydrogenase, phenylacetic acid degradation, and the glycolate/glyoxylate utilization pathway. Our results suggest that metabolic changes in the Bvg(-) mode may be participating in bacterial survival, transmission, and/or persistence and identify over 200 new s that can be tested for function. Within the past 20 years, outbreaks of whooping cough, caused by , have led to respiratory disease and infant mortalities, despite good vaccination coverage. This is due, at least in part, to the introduction of a less effective acellular vaccine in the 1990s. It is crucial, then, to understand the molecular basis of growth and infection. The two-component system BvgA (response regulator)/BvgS (histidine kinase) is the master regulator of virulence genes. We report here the first RNA-seq analysis of the BvgAS regulon in , revealing that more than 550 genes are regulated by BvgAS. We show that genes for multiple and varied metabolic pathways are highly regulated in the Bvg(-) mode (absence of BvgA phosphorylation). Our results suggest that metabolic changes in the Bvg(-) mode may be participating in bacterial survival, transmission, and/or persistence.
Topics: Bacterial Proteins; Bordetella pertussis; Gene Expression Regulation, Bacterial; Genes, Regulator; High-Throughput Nucleotide Sequencing; Promoter Regions, Genetic; Regulon; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcription Factors; Transcriptome; Virulence
PubMed: 29018122
DOI: 10.1128/mBio.01526-17 -
Proceedings of the National Academy of... Mar 2016The BvgAS phosphorelay regulates ∼10% of the annotated genomes of Bordetella pertussis and Bordetella bronchiseptica and controls their infectious cycles. The...
The BvgAS phosphorelay regulates ∼10% of the annotated genomes of Bordetella pertussis and Bordetella bronchiseptica and controls their infectious cycles. The hierarchical organization of the regulatory network allows the integration of contextual signals to control all or specific subsets of BvgAS-regulated genes. Here, we characterize a regulatory node involving a type III secretion system (T3SS)-exported protein, BtrA, and demonstrate its role in determining fundamental differences in T3SS phenotypes among Bordetella species. We show that BtrA binds and antagonizes BtrS, a BvgAS-regulated extracytoplasmic function (ECF) sigma factor, to couple the secretory activity of the T3SS apparatus to gene expression. In B. bronchiseptica, a remarkable spectrum of expression states can be resolved by manipulating btrA, encompassing over 80 BtrA-activated loci that include genes encoding toxins, adhesins, and other cell surface proteins, and over 200 BtrA-repressed genes that encode T3SS apparatus components, secretion substrates, the BteA effector, and numerous additional factors. In B. pertussis, BtrA retains activity as a BtrS antagonist and exerts tight negative control over T3SS genes. Most importantly, deletion of btrA in B. pertussis revealed T3SS-mediated, BteA-dependent cytotoxicity, which had previously eluded detection. This effect was observed in laboratory strains and in clinical isolates from a recent California pertussis epidemic. We propose that the BtrA-BtrS regulatory node determines subspecies-specific differences in T3SS expression among Bordetella species and that B. pertussis is capable of expressing a full range of T3SS-dependent phenotypes in the presence of appropriate contextual cues.
Topics: Bordetella bronchiseptica; Bordetella pertussis; Genes, Bacterial; Sigma Factor; Virulence
PubMed: 26884180
DOI: 10.1073/pnas.1600320113 -
Scientific Reports Apr 2018Several species of the Gram-negative genus Bordetella are the cause of respiratory infections in mammals and birds, including whooping cough (pertussis) in humans. Very...
Several species of the Gram-negative genus Bordetella are the cause of respiratory infections in mammals and birds, including whooping cough (pertussis) in humans. Very recently, a novel atypical species, Bordetella pseudohinzii, was isolated from laboratory mice. These mice presented no obvious clinical symptoms but elevated numbers of neutrophils in bronchoalveolar lavage fluid and inflammatory signs in histopathology. We noted that this species can occur at high prevalence in a mouse facility despite regular pathogen testing according to the FELASA-recommendations. Affected C57BL/6 J mice had, in addition to the reported pulmonary alterations, tracheal inflammation with reduced numbers of ciliated cells, slower ciliary beat frequency, and largely (>50%) compromised cilia-driven particle transport speed on the mucosal surface, a primary innate defence mechanism. In an in vitro-model, Bordetella pseudohinzii attached to respiratory kinocilia, impaired ciliary function within 4 h and caused epithelial damage within 24 h. Regular testing for this ciliotropic Bordetella species and excluding it from colonies that provide mice for lung research shall be recommended. On the other hand, controlled colonization and infection with Bordetella pseudohinzii may serve as an experimental model to investigate mechanisms of mucociliary clearance and microbial strategies to escape from this primary innate defence response.
Topics: Animals; Bordetella; Bordetella Infections; Cilia; DNA, Bacterial; Mice; Mice, Inbred C57BL; Mucociliary Clearance; Respiratory Tract Infections; Rodent Diseases; Sequence Analysis, DNA; Trachea
PubMed: 29632402
DOI: 10.1038/s41598-018-23830-4 -
Journal of Clinical Microbiology Dec 2020Detection of and using molecular methods is sensitive and specific with a short turnaround time compared to other diagnostic methods. In this multicenter study, we...
Detection of and using molecular methods is sensitive and specific with a short turnaround time compared to other diagnostic methods. In this multicenter study, we compared the performance of the Simplexa Bordetella Direct kit to those of other molecular assays in detecting and differentiating and in nasopharyngeal swab specimens. The limits of detection (LODs) were 150 CFU/ml or 3 fg/μl of DNA for and 1,500 CFU/ml or 10 fg/μl of DNA for A total of 1,103 fresh and residual frozen specimens from eight clinical sites were tested. Combining the data from individual clinical sites using different comparative assays, the overall positive percent agreement (PPA) and negative percent agreement (NPA) for were 98.7% and 97.3%, respectively. The overall PPA and NPA for were 96.7% and 100%, respectively. For prospective fresh specimens, the overall PPA and NPA for both targets were 97.7% and 99.3%, respectively. For retrospective frozen specimens, the overall PPA and NPA for both targets were 92.6% and 93.2%, respectively. The percentage of invalid results was 1.0%. A cross-reactivity study using 74 non- bacterial species and five yeast species revealed that the Simplexa Bordetella Direct kit was 100% specific. The hands-on time and assay run time of the Simplexa Bordetella Direct kit are favorable compared to those of other commercial and laboratory-developed tests. In summary, the Simplexa Bordetella Direct kit has a performance comparable to those of other molecular assays for the detection of and .
Topics: Bordetella; Bordetella Infections; Bordetella parapertussis; Bordetella pertussis; Humans; Nasopharynx; Prospective Studies; Retrospective Studies; Whooping Cough
PubMed: 33055187
DOI: 10.1128/JCM.01041-20 -
Microbiology Spectrum Mar 2019Bacteria use a variety of mechanisms to translocate proteins from the cytoplasm, where they are synthesized, to the cell surface or extracellular environment or directly... (Review)
Review
Bacteria use a variety of mechanisms to translocate proteins from the cytoplasm, where they are synthesized, to the cell surface or extracellular environment or directly into other cells, where they perform their ultimate functions. Type V secretion systems (T5SS) use β-barrel transporter domains to export passenger domains across the outer membranes of Gram-negative bacteria. Distinct among T5SS are type Vb or two-partner secretion (TPS) systems in which the transporter and passenger are separate proteins, necessitating a mechanism for passenger-translocator recognition in the periplasm and providing the potential for reuse of the translocator. This review describes current knowledge of the TPS translocation mechanism, using filamentous hemagglutinin (FHA) and its transporter FhaC as a model. We present the hypothesis that the TPS pathway may be a general mechanism for contact-dependent delivery of toxins to target cells.
Topics: Adhesins, Bacterial; Bacterial Outer Membrane Proteins; Bordetella; Bordetella pertussis; Gram-Negative Bacteria; Hemagglutinins; Membrane Transport Proteins; Models, Molecular; Secretory Pathway; Type V Secretion Systems; Virulence; Virulence Factors, Bordetella; Whooping Cough
PubMed: 30927348
DOI: 10.1128/microbiolspec.PSIB-0024-2018 -
Journal of Clinical Microbiology Feb 2019Molecular methods offer superior sensitivity and specificity and reduce testing turnaround time from days to hours for detection of and In this study, we evaluated the...
Molecular methods offer superior sensitivity and specificity and reduce testing turnaround time from days to hours for detection of and In this study, we evaluated the performance of the automated PCR-based Aries Assay, which detects both and directly from nasopharyngeal swab specimens. The limits of detection (LoDs) were 1,800 CFU·ml for and 213 CFU·ml for The assay detected 16/18 unique / strains. Of 71 potentially cross-reacting organisms, 5 generated false positives in 1/6 replicates; none of 6 additional spp. were erroneously detected. Specimens were stable at 20 to 25°C for at least 10 h, at 4 to 8°C for 10 days, and at temperatures not exceeding -70°C for 6 months. Of 1,052 nasopharyngeal specimens from patients with suspected pertussis, 3.0% ( = 32) were positive and 0.2% ( = 2) were positive. Combining these data with Aries Assay data from 57 nasopharyngeal samples with previously confirmed or data and with data from 50 contrived samples, the proportions of positive and negative agreement of the respective Aries assays with the reference assays were 97.1% and 99.0% for and 100% and 99.7% for The Aries Assay provides accurate detection and distinction of and infections within 2 h. (This study has been registered at ClinicalTrials.gov under registration no. NCT02862262.).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Automation, Laboratory; Bordetella Infections; Bordetella parapertussis; Bordetella pertussis; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Molecular Diagnostic Techniques; Nasopharynx; Polymerase Chain Reaction; Prospective Studies; Sensitivity and Specificity; Time Factors; Young Adult
PubMed: 30518543
DOI: 10.1128/JCM.01471-18