-
MBio Jun 2022What causes the cough in whooping cough (pertussis) has been a longstanding question in the field but has been difficult to answer because of the perceived lack of...
What causes the cough in whooping cough (pertussis) has been a longstanding question in the field but has been difficult to answer because of the perceived lack of convenient small animal models. Y. Hiramatsu, K. Suzuki, T. Nishida, N. Onoda, et al. (mBio 13:e01397-21, 2022, https://doi.org/10.1128/mbio.03197-21) used a mouse model and cellular studies to investigate bacterial and host factors that contribute to cough production during Bordetella pertussis infection. In elegant studies, they found that the bacterial factors pertussis toxin, lipooligosaccharide, and Vag8 function cooperatively to produce cough. These factors induce production of host bradykinin, a known cough inducer that sensitizes the ion channel TRPV1 on neurons, and they investigated host signaling pathways altered by the bacterial factors that exacerbate cough responses. This is a highly significant and important finding that not only elucidates mechanisms underlying the pathophysiology of the severe cough, but also may reveal potential novel therapeutic approaches to treat individuals suffering from the debilitating effects of cough in pertussis.
Topics: Animals; Bordetella Infections; Bordetella pertussis; Cough; Mice; Whooping Cough
PubMed: 35604095
DOI: 10.1128/mbio.00917-22 -
Microbial Genomics Dec 2023Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32...
Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32 isolates sourced from three different surveillance programmes in South Africa between 2015 and 2019. Genome sequences were characterized using multilocus sequence typing, vaccine antigen genes (, , , and ) and overall genome structure. All isolates were sequence type 2 and harboured the pertussis toxin promoter allele . The dominant genotype was 3122 (31/32, 96.9 %), with no pertactin-deficient or other mutations in vaccine antigen genes identified. Amongst 21 isolates yielding closed genome assemblies, eight distinct genome structures were detected, with 61.9 % (13/21) of the isolates exhibiting three predominant structures. Increases in case numbers are probably not due to evolutionary changes in the genome but possibly due to other factors such as the cyclical nature of disease, waning immunity due to the use of acellular vaccines and/or population immunity gaps.
Topics: Humans; Bordetella pertussis; Whooping Cough; South Africa; Pertussis Vaccine; Genomics
PubMed: 38117675
DOI: 10.1099/mgen.0.001162 -
Emerging Infectious Diseases Oct 2020Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a...
Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a macrolide-resistant mutation, A2047G, in the 23S rRNA. We identified the MT104 genotype of macrolide-resistant B. pertussis (which is prevalent in mainland China) and its variants in these patients.
Topics: Anti-Bacterial Agents; Bordetella pertussis; China; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; RNA, Ribosomal, 23S; Vietnam
PubMed: 32946738
DOI: 10.3201/eid2610.201035 -
Pathogens and Disease Nov 2015Pertussis, or whooping cough, is a highly contagious respiratory disease that is caused by the Gram-negative bacterium Bordetella pertussis, which is transmitted... (Review)
Review
Pertussis, or whooping cough, is a highly contagious respiratory disease that is caused by the Gram-negative bacterium Bordetella pertussis, which is transmitted exclusively from human to human. While vaccination against B. pertussis has been successful, replacement of the whole cell vaccine with an acellular component vaccine has correlated with reemergence of the disease, especially in adolescents and infants. Based on their presumed importance in mediating adherence to host tissues, filamentous hemagglutinin (FHA) and fimbria (FIM) were selected as components of most acellular pertussis vaccines. In this review, we describe the biogenesis of FHA and FIM, recent data that show that these factors do, in fact, play critical roles in adherence to respiratory epithelium, and evidence that they also contribute to persistence in the lower respiratory tract by modulating the host immune response. We also discuss shortcomings of whole cell and acellular pertussis vaccines and the possibility that FHA and FIM could serve as effective protective antigens in next-generation vaccines.
Topics: Adhesins, Bacterial; Bacterial Adhesion; Bordetella pertussis; Fimbriae, Bacterial; Humans; Pertussis Vaccine; Virulence Factors, Bordetella
PubMed: 26416077
DOI: 10.1093/femspd/ftv079 -
Antioxidants & Redox Signaling Feb 2020Structural and functional characterization of the globin-coupled sensors (GCSs) from (GReg) and (GReg). Ultraviolet/visible and resonance Raman spectroscopies...
Structural and functional characterization of the globin-coupled sensors (GCSs) from (GReg) and (GReg). Ultraviolet/visible and resonance Raman spectroscopies confirm the presence in GReg and GReg of a globin domain capable of reversible gaseous ligand binding. In GReg, an influence of the transmitter domain on the heme proximal region of the globin domain can be seen, and ' is higher than for other GCSs. The O binding kinetics suggests the presence of an open and a closed conformation. As for GReg, the fully oxygenated GReg show a very high diguanylate cyclase activity. The carbon monoxide rebinding to GReg indicates that intra- and intermolecular interactions influence the ligand binding. The globin domains of both proteins (GReg globin domain and GRegGb with cysteines (Cys16, 45, 114, 154) mutated to serines [GReg-Gb*]) share the same GCS fold, a similar proximal but a different distal side structure. They homodimerize through a G-H helical bundle as in other GCSs. However, GReg-Gb* shows also a second dimerization mode. This article extends our knowledge on the GCS proteins and contributes to a better understanding of the GCSs role in the formation of bacterial biofilms. GReg and GReg conform to the GCS family, share a similar overall structure, but they have different properties in terms of the ligand binding. In particular, GReg shows an open and a closed conformation that in the latter form will very tightly bind oxygen. GReg has only one closed conformation. In both proteins, it is the fully oxygenated GCS form that catalyzes the production of the second messenger.
Topics: Azotobacter vinelandii; Bacterial Proteins; Binding Sites; Bordetella pertussis; Globins; Heme-Binding Proteins; Protein Structure, Quaternary; Protein Structure, Tertiary; Structure-Activity Relationship
PubMed: 31559835
DOI: 10.1089/ars.2018.7690 -
Emerging Infectious Diseases Mar 2021Pertussis is a vaccine-preventable disease, and its recent resurgence might be attributable to the emergence of strains that differ genetically from the vaccine strain....
Pertussis is a vaccine-preventable disease, and its recent resurgence might be attributable to the emergence of strains that differ genetically from the vaccine strain. We describe a novel pertussis isolate-based surveillance system and a core genome multilocus sequence typing scheme to assess Bordetella pertussis genetic variability and investigate the increased incidence of pertussis in Austria. During 2018-2020, we obtained 123 B. pertussis isolates and typed them with the new scheme (2,983 targets and preliminary cluster threshold of <6 alleles). B. pertussis isolates in Austria differed genetically from the vaccine strain, both in their core genomes and in their vaccine antigen genes; 31.7% of the isolates were pertactin-deficient. We detected 8 clusters, 1 of them with pertactin-deficient isolates and possibly part of a local outbreak. National expansion of the isolate-based surveillance system is needed to implement pertussis-control strategies.
Topics: Alleles; Austria; Bacterial Outer Membrane Proteins; Bordetella pertussis; Humans; Pertussis Vaccine; Virulence Factors, Bordetella; Whooping Cough
PubMed: 33622477
DOI: 10.3201/eid2703.202314 -
Journal of Medical Microbiology Oct 2021Whooping cough (pertussis) is a highly contagious respiratory bacterial infection caused by and is an important cause of morbidity and mortality worldwide, particularly...
Whooping cough (pertussis) is a highly contagious respiratory bacterial infection caused by and is an important cause of morbidity and mortality worldwide, particularly in infants. can cause a similar, but usually less severe pertussis-like disease. has a number of virulence factors including adhesins and toxins which allow the organism to bind to ciliated epithelial cells in the upper respiratory tract and interfere with host clearance mechanisms. Typical symptoms of pertussis include paroxysmal cough with characteristic whoop and vomiting. Severe complications and deaths occur mostly in infants. Laboratory confirmation can be performed by isolation, detection of genomic DNA or specific antibodies. Childhood vaccination is safe, effective and remains the best control method available. Many countries have replaced whole-cell pertussis vaccines (wP) with acellular pertussis vaccines (aP). Waning protection following immunisation with aP is considered to be more rapid than that from wP. Deployed by resource-rich countries to date, maternal immunisation programmes have also demonstrated high efficacy in preventing hospitalisation and death in infants by passive immunisation through transplacental transfer of maternal antibodies.
Topics: Bordetella parapertussis; Bordetella pertussis; Humans; Infant; Pertussis Vaccine; Virulence Factors; Whooping Cough
PubMed: 34668853
DOI: 10.1099/jmm.0.001442 -
Nucleic Acids Research Jan 2021Diversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the...
Diversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the human microbiome and the microbial 'dark matter'. Variation occurs through adenine-mutagenesis, in which genetic information in RNA is reverse transcribed faithfully to cDNA for all template bases but adenine. We investigated the determinants of adenine-mutagenesis in the prototypical Bordetella bacteriophage DGR through an in vitro system composed of the reverse transcriptase bRT, Avd protein, and a specific RNA. We found that the catalytic efficiency for correct incorporation during reverse transcription by the bRT-Avd complex was strikingly low for all template bases, with the lowest occurring for adenine. Misincorporation across a template adenine was only somewhat lower in efficiency than correct incorporation. We found that the C6, but not the N1 or C2, purine substituent was a key determinant of adenine-mutagenesis. bRT-Avd was insensitive to the C6 amine of adenine but recognized the C6 carbonyl of guanine. We also identified two bRT amino acids predicted to nonspecifically contact incoming dNTPs, R74 and I181, as promoters of adenine-mutagenesis. Our results suggest that the overall low catalytic efficiency of bRT-Avd is intimately tied to its ability to carry out adenine-mutagenesis.
Topics: Adenine; Arginine; Bacteriophages; Base Sequence; Bordetella; Catalysis; Cell-Free System; Computer Simulation; DNA, Complementary; Glycine; High-Throughput Nucleotide Sequencing; Models, Molecular; Mutagenesis; Protein Conformation; RNA-Directed DNA Polymerase; Recombinant Proteins; Retroelements
PubMed: 33367793
DOI: 10.1093/nar/gkaa1240 -
MBio May 2019encodes and expresses a flagellar apparatus. In contrast, , the causative agent of whooping cough, has historically been described as a nonmotile and nonflagellated...
encodes and expresses a flagellar apparatus. In contrast, , the causative agent of whooping cough, has historically been described as a nonmotile and nonflagellated organism. The previous statements that was a nonmotile organism were consistent with a stop codon located in the flagellar biosynthesis gene, , discovered when the Tohama I genome was sequenced and analyzed by Parkhill et al. in 2003 (J. Parkhill, M. Sebaihia, A. Preston, L. D. Murphy, et al., Nat Genet, 35:32-40, 2003, https://doi.org/10.1038/ng1227). The stop codon has subsequently been found in all annotated genomes. Parkhill et al. also showed, however, that contains all genetic material required for flagellar synthesis and function. We and others have determined by various transcriptomic analyses that these flagellar genes are differentially regulated under a variety of growth conditions. In light of these data, we tested for motility and found that both laboratory-adapted strains and clinical isolates can be motile. Upon isolation of motile , we discovered flagellum-like structures on the surface of the bacteria. motility appears to occur primarily in the Bvg(-) phase, consistent with regulation present in Motility can also be induced by the presence of fetal bovine serum. These observations demonstrate that can express flagellum-like structures, and although it remains to be determined if expresses flagella during infection or if motility and/or flagella play roles during the cycle of infection and transmission, it is clear that these data warrant further investigation. This report provides evidence for motility and expression of flagella by , a bacterium that has been reported as nonmotile since it was first isolated and studied. As with , cells can express and assemble a flagellum-like structure on their surface, which in other organisms has been implicated in several important processes that occur The discovery that is motile raises many questions, including those regarding the mechanisms of regulation for flagellar gene and protein expression and, importantly, the role of flagella during infection. This novel observation provides a foundation for further study of flagella and motility in the contexts of infection and transmission.
Topics: Bordetella bronchiseptica; Bordetella pertussis; Flagella; Flagellin; Gene Expression Regulation, Bacterial; Movement
PubMed: 31088927
DOI: 10.1128/mBio.00787-19 -
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