scholarly journals Global Population Structure and Evolution of Bordetella pertussis and Their Relationship with Vaccination

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Marieke J. Bart ◽  
Simon R. Harris ◽  
Abdolreza Advani ◽  
Yoshichika Arakawa ◽  
Daniela Bottero ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Vaccine Coverage ◽  
Physiological Role ◽  
Toxin Production ◽  
Content Type ◽  
Vaccine Introduction ◽  
Worldwide Population ◽  
Genes Encoding ◽  
Acellular Vaccines

ABSTRACTBordetella pertussiscauses pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343B. pertussisstrains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in whichB. pertussisand the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines.IMPORTANCEWhooping cough is mainly caused byBordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343B. pertussisisolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population ofB. pertussisis evolving in response to vaccine introduction, potentially enabling vaccine escape.

scholarly journals Probing the Genome-Scale Metabolic Landscape of Bordetella pertussis, the Causative Agent of Whooping Cough

2017 ◽  
Vol 83 (21) ◽  
Author(s):  
Filipe Branco dos Santos ◽  
Brett G. Olivier ◽  
Joost Boele ◽  
Vincent Smessaert ◽  
Philippe De Rop ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Experimental Validation ◽  
Whooping Cough ◽  
Tca Cycle ◽  
Metabolic Model ◽  
Toxin Production ◽  
Metabolic Reconstruction ◽  
Growth Media ◽  
Content Type ◽  
Genome Scale

ABSTRACT Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis. Despite widespread vaccination, its incidence has been rising alarmingly, and yet, the physiology of B. pertussis remains poorly understood. We combined genome-scale metabolic reconstruction, a novel optimization algorithm, and experimental data to probe the full metabolic potential of this pathogen, using B. pertussis strain Tohama I as a reference. Experimental validation showed that B. pertussis secretes a significant proportion of nitrogen as arginine and purine nucleosides, which may contribute to modulation of the host response. We also found that B. pertussis can be unexpectedly versatile, being able to metabolize many compounds while displaying minimal nutrient requirements. It can grow without cysteine, using inorganic sulfur sources, such as thiosulfate, and it can grow on organic acids, such as citrate or lactate, as sole carbon sources, providing in vivo demonstration that its tricarboxylic acid (TCA) cycle is functional. Although the metabolic reconstruction of eight additional strains indicates that the structural genes underlying this metabolic flexibility are widespread, experimental validation suggests a role of strain-specific regulatory mechanisms in shaping metabolic capabilities. Among five alternative strains tested, three strains were shown to grow on substrate combinations requiring a functional TCA cycle, but only one strain could use thiosulfate. Finally, the metabolic model was used to rationally design growth media with >2-fold improvements in pertussis toxin production. This study thus provides novel insights into B. pertussis physiology and highlights the potential, but also the limitations, of models based solely on metabolic gene content. IMPORTANCE The metabolic capabilities of Bordetella pertussis, the causative agent of whooping cough, were investigated from a systems-level perspective. We constructed a comprehensive genome-scale metabolic model for B. pertussis and challenged its predictions experimentally. This systems approach shed light on new potential host-microbe interactions and allowed us to rationally design novel growth media with >2-fold improvements in pertussis toxin production. Most importantly, we also uncovered the potential for metabolic flexibility of B. pertussis (significantly larger range of substrates than previously alleged; novel active pathways allowing growth in minimal, nearly mineral nutrient combinations where only the carbon source must be organic), although our results also highlight the importance of strain-specific regulatory determinants in shaping metabolic capabilities. Deciphering the underlying regulatory mechanisms appears to be crucial for a comprehensive understanding of B. pertussis's lifestyle and the epidemiology of whooping cough. The contribution of metabolic models in this context will require the extension of the genome-scale metabolic model to integrate this regulatory dimension.

scholarly journals Bordetella pertussis Lipid A Glucosamine Modification Confers Resistance to Cationic Antimicrobial Peptides and Increases Resistance to Outer Membrane Perturbation

2014 ◽  
Vol 58 (8) ◽  
pp. 4931-4934 ◽  
Author(s):  
Nita R. Shah ◽  
Robert E. W. Hancock ◽  
Rachel C. Fernandez
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Outer Membrane ◽  
Bordetella Pertussis ◽  
Lipid A ◽  
Whooping Cough ◽  
Human Immune System ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Membrane Perturbation

ABSTRACTBordetella pertussis, the causative agent of whooping cough, has many strategies for evading the human immune system. Lipopolysaccharide (LPS) is an important Gram-negative bacterial surface structure that activates the immune system via Toll-like receptor 4 and enables susceptibility to cationic antimicrobial peptides (CAMPs). We show modification of the lipid A region of LPS with glucosamine increased resistance to numerous CAMPs, including LL-37. Furthermore, we demonstrate that this glucosamine modification increased resistance to outer membrane perturbation.

The immunology of Bordetella pertussis infection and vaccination

Pertussis ◽  
2018 ◽  
pp. 42-65
Author(s):  
Mieszko M. Wilk ◽  
Aideen C. Allen ◽  
Alicja Misiak ◽  
Lisa Borkner ◽  
Kingston H.G. Mills
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Vaccine Coverage ◽  
Immunological Memory ◽  
Nasal Colonization ◽  
Pertussis Infection ◽  
Genetic Changes ◽  
Antibody Titres ◽  
Previous Infection ◽  
Cellular Immune

Bordetella pertussis causes whooping cough (pertussis), a severe and sometimes fatal respiratory infectious disease, especially in young infants. Pertussis can be prevented in infants and children by immunization with either whole-cell pertussis (wP) or acellular pertussis (aP) vaccines; however, its incidence is increasing in many countries despite high vaccine coverage. This resurgence in populations immunized with aP vaccines has been attributed to (1) genetic changes in circulating strains of B. pertussis resulting from vaccine-driven immune selection, (2) waning protective immunity due to poor induction of immunological memory, or (3) a failure of aP vaccines to induce the appropriate arm(s) of the cellular immune responses required to prevent infection. Studies in a baboon model have suggested that previous infection prevents reinfection as well as disease, whereas aP vaccines fail to prevent nasal colonization and transmission of B. pertussis. Studies in the mouse model have demonstrated that immunization with wP vaccines induces Th1 and Th17 responses, whereas aP vaccines promote Th2-skewed responses and high antibody titres. Thus, while aP vaccine-induced antibodies may prevent pertussis, they may not prevent nasal colonization or transmission. Emerging data have suggested that replacing alum with novel adjuvants based on pathogen-associated molecular patterns has the capacity to switch the responses induced with aP vaccines to the more protective Th1/Th17 responses and may also enhance immunological memory. It is likely that third-generation pertussis vaccines will be based on live attenuated bacteria or aP formulations with novel adjuvants, which prevent nasal and lung infection and induce sustained immunity through induction of memory T cells.

Bordetella infection

2020 ◽  
pp. 1073-1076
Author(s):  
Cameron C. Grant
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Severe Disease ◽  
Diagnostic Methods ◽  
Illness Onset ◽  
Young Infants ◽  
Adolescents And Adults ◽  
Risk Of Exposure ◽  
Acellular Vaccines ◽  
Infectious Organism

Bordetella are small Gram-negative coccobacilli, of which Bordetella pertussis is the most important human pathogen. Bordetella pertussis is the cause of whooping cough, which remains one of the 10 leading causes of death among children less than five years old. Transmission of this highly infectious organism is primarily by aerosolized droplets. The preferred diagnostic methods are polymerase chain reaction detection from nasopharyngeal samples and serology (IgG antibodies to pertussis toxin). Macrolide antibiotics are recommended if started within four weeks of illness onset. Preventing severe disease in young children remains the primary goal, hence schedules consist of a three-dose infant series and subsequent booster doses. Acellular vaccines enable immunization schedules to include adolescents and adults. Acellular pertussis vaccine given to pregnant women reduces the risk of pertussis in young infants. Antibiotic prophylaxis is given when there is an infant at risk of exposure.

scholarly journals The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

2013 ◽  
Vol 81 (11) ◽  
pp. 4081-4090 ◽  
Author(s):  
Ilona Bibova ◽  
Karolina Skopova ◽  
Jiri Masin ◽  
Ondrej Cerny ◽  
David Hot ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Posttranscriptional Regulation ◽  
Noncoding Rna ◽  
Whooping Cough ◽  
Lethal Dose ◽  
Rna Chaperone ◽  
Content Type ◽  
Small Noncoding Rna ◽  
Mrna Targets

ABSTRACTBordetella pertussisis a Gram-negative pathogen causing the human respiratory disease called pertussis or whooping cough. Here we examined the role of the RNA chaperone Hfq inB. pertussisvirulence. Hfq mediates interactions between small regulatory RNAs and their mRNA targets and thus plays an important role in posttranscriptional regulation of many cellular processes in bacteria, including production of virulence factors. We characterized anhfqdeletion mutant (Δhfq) ofB. pertussis18323 and show that the Δhfqstrain produces decreased amounts of the adenylate cyclase toxin that plays a central role inB. pertussisvirulence. Production of pertussis toxin and filamentous hemagglutinin was affected to a lesser extent.In vitro, the ability of the Δhfqstrain to survive within macrophages was significantly reduced compared to that of the wild-type (wt) strain. The virulence of the Δhfqstrain in the mouse respiratory model of infection was attenuated, with its capacity to colonize mouse lungs being strongly reduced and its 50% lethal dose value being increased by one order of magnitude over that of the wt strain. In mixed-infection experiments, the Δhfqstrain was then clearly outcompeted by the wt strain. This requirement for Hfq suggests involvement of small noncoding RNA regulation inB. pertussisvirulence.

scholarly journals Phosphoserine Phosphatase Is Required for Serine and One-Carbon Unit Synthesis in Hydrogenobacter thermophilus

2017 ◽  
Vol 199 (21) ◽  
Author(s):  
Keugtae Kim ◽  
Yoko Chiba ◽  
Azusa Kobayashi ◽  
Hiroyuki Arai ◽  
Masaharu Ishii
Keyword(s):  
Physiological Role ◽  
Tca Cycle ◽  
Content Type ◽  
Phosphoserine Phosphatase ◽  
Genes Encoding ◽  
Hydrogenobacter Thermophilus ◽  
Glycine Cleavage ◽  
Major Donor ◽  
Serine Biosynthesis

ABSTRACT Hydrogenobacter thermophilus is an obligate chemolithoautotrophic bacterium of the phylum Aquificae and is capable of fixing carbon dioxide through the reductive tricarboxylic acid (TCA) cycle. The recent discovery of two novel-type phosphoserine phosphatases (PSPs) in H. thermophilus suggests the presence of a phosphorylated serine biosynthesis pathway; however, the physiological role of these novel-type metal-independent PSPs (iPSPs) in H. thermophilus has not been confirmed. In the present study, a mutant strain with a deletion of pspA, the catalytic subunit of iPSPs, was constructed and characterized. The generated mutant was a serine auxotroph, suggesting that the novel-type PSPs and phosphorylated serine synthesis pathway are essential for serine anabolism in H. thermophilus. As an autotrophic medium supplemented with glycine did not support the growth of the mutant, the reversible enzyme serine hydroxymethyltransferase does not appear to synthesize serine from glycine and may therefore generate glycine and 5,10-CH2-tetrahydrofolate (5,10-CH2-THF) from serine. This speculation is supported by the lack of glycine cleavage activity, which is needed to generate 5,10-CH2-THF, in H. thermophilus. Determining the mechanism of 5,10-CH2-THF synthesis is important for understanding the fundamental anabolic pathways of organisms, because 5,10-CH2-THF is a major one-carbon donor that is used for the synthesis of various essential compounds, including nucleic and amino acids. The findings from the present experiments using a pspA deletion mutant have confirmed the physiological role of iPSPs as serine producers and show that serine is a major donor of one-carbon units in H. thermophilus. IMPORTANCE Serine biosynthesis and catabolism pathways are intimately related to the metabolism of 5,10-CH2-THF, a one-carbon donor that is utilized for the biosynthesis of various essential compounds. For this reason, determining the mechanism of serine synthesis is important for understanding the fundamental anabolic pathways of microorganisms. In the present study, we experimentally confirmed that a novel phosphoserine phosphatase in the obligate chemolithoautotrophic bacterium Hydrogenobacter thermophilus is essential for serine biosynthesis. This finding indicates that serine is synthesized from an intermediate of gluconeogenesis in H. thermophilus. In addition, because glycine cleavage system activity and genes encoding an enzyme capable of producing 5,10-CH2-THF were not detected, serine appears to be the major one-carbon donor to tetrahydrofolate (THF) in H. thermophilus.

scholarly journals BspR/BtrA, an Anti-σ Factor, Regulates the Ability ofBordetella bronchisepticaTo Cause Cough in Rats

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Keiji Nakamura ◽  
Noriko Shinoda ◽  
Yukihiro Hiramatsu ◽  
Shinya Ohnishi ◽  
Shigeki Kamitani ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Bordetella Pertussis ◽  
Rat Model ◽  
Whooping Cough ◽  
Respiratory Infections ◽  
Wild Type ◽  
Content Type ◽  
Infection Models ◽  
Natural Hosts ◽  
Σ Factor

ABSTRACTBordetella pertussis,B. parapertussis, andB. bronchisepticacause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals that replicate coughing afterBordetellainfection. Here, we present a coughing model of rats infected withB. bronchiseptica. Rats, which are one of natural hosts ofB. bronchiseptica, were readily infected with the organisms and showed frequent coughing.B. pertussisalso caused coughing in rats, which is consistent with previous reports, but the cough response was less apparent than theB. bronchiseptica-induced cough. By using the rat model, we demonstrated that adenylate cyclase toxin, dermonecrotic toxin, and the type III secretion system are not involved in cough production, but BspR/BtrA (different names for the same protein), an anti-σ factor, regulates the production of unknown factor(s) to cause coughing. Rat coughing was observed by inoculation of not only the living bacteria but also the bacterial lysates. Infection withbspR(btrA)-deficient strains caused significantly less frequent coughing than the wild type; however, intranasal inoculation of the lysates from abspR(btrA)-deficient strain caused coughing similarly to the wild type, suggesting that BspR/BtrA regulates the production of the cough factor(s) only when the bacteria colonize host bodies. Moreover, the cough factor(s) was found to be heat labile and produced byB. bronchisepticain the Bvg+phase. We consider that our rat model provides insight into the pathogenesis of cough induced by theBordetellainfection.IMPORTANCEWhooping cough is a contagious respiratory disease caused byBordetella pertussis. This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzingBordetella-induced coughing is the lack of conventional animal models that replicate coughing. AsBordetella pertussisis highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected withB. bronchiseptica, which shares many virulence factors withB. pertussis. Using this rat model, we demonstrated that some of the major virulence factors ofBordetellaare not involved in cough production, but an anti-σ factor, BspR/BtrA, ofB. bronchisepticaregulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by whichBordetellainduces cough.

Vaccine-driven selection and the changing molecular epidemiology of Bordetella pertussis

Pertussis ◽  
2018 ◽  
pp. 166-181
Author(s):  
Ruiting Lan ◽  
Sophie Octavia
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Vaccine Coverage ◽  
Toxin Production ◽  
Developed Countries ◽  
Single Nucleotide ◽  
Genetic Changes ◽  
Vaccine Preventable Diseases ◽  
Acellular Vaccine

Pertussis remains one of the least controlled vaccine-preventable diseases despite high vaccine coverage in many countries. There are ongoing debates about the causes of its resurgence. Major changes have occurred in the Bordetella pertussis population since the introduction of vaccination. Currently circulating strains in Australia and many other developed countries are grouped in single nucleotide polymorphism (SNP) cluster I (also known as ptxP3 strains). The emergence and expansion of SNP cluster I has been associated with two major genetic changes in B. pertussis: a change in its pertussis toxin promoter (to ptxP3) which leads to increased pertussis toxin production and the change of the acellular vaccine pertactin gene allele to prn2. More recently, strains that lack pertactin have emerged independently in different lineages. The resurgence of pertussis in highly vaccinated populations can be, at least in part, explained by genetic changes that increase the fitness of circulating B. pertussis strains.

scholarly journals Genetic, Biochemical, and Serological Characterization of a New Pneumococcal Serotype, 6H, and Generation of a Pneumococcal Strain Producing Three Different Capsular Repeat Units

2015 ◽  
Vol 22 (3) ◽  
pp. 313-318 ◽  
Author(s):  
In Ho Park ◽  
K. Aaron Geno ◽  
Jigui Yu ◽  
Melissa B. Oliver ◽  
Kyung-Hyo Kim ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Vaccine Coverage ◽  
Repeat Unit ◽  
Enzyme Specificity ◽  
Content Type ◽  
Repeat Units ◽  
Novel Approach ◽  
Serological Characterization ◽  
Pneumococcal Strain ◽  
Genes Encoding

ABSTRACTStreptococcus pneumoniaeclinical isolates were recently described that produced capsular polysaccharide with properties of both serotypes 6A and 6B. Their hybrid serological property correlated with mutations affecting the glycosyltransferase WciP, which links rhamnose to ribitol by an α(1-3) linkage for serotypes 6A and 6C and an α(1-4) linkage for serotypes 6B and 6D. The isolates had mutations in the triad residues of WciP that have been correlated with enzyme specificity. The canonical triad residues of WciP are Ala192-Ser195-Arg254 for serotypes 6A and 6C and Ser192-Asn195-Gly254 for serotypes 6B and 6D. To prove that the mutations in the triad residues are responsible for the hybrid serotype, we introduced the previously described Ala192-Cys195-Arg254 triad into a 6A strain and found that the change made WciP bispecific, resulting in 6A and 6B repeat unit expression, although 6B repeat unit production was favored over production of 6A repeat units. Likewise, this triad permitted a 6C strain to express 6C and 6D repeat units. With reported bispecificity in WciN, which adds either glucose or galactose as the second sugar in the serogroup 6 repeat unit, the possibility exists for a strain to simultaneously produce all four serogroup 6 repeat units; however, when genes encoding both bispecific enzymes were introduced into a 6A strain, only 6A, 6B, and 6D repeat units were detected serologically. Nonetheless, this may be the first example of a bacterial polysaccharide with three different repeat units. This strategy of expressing multiple repeat units in a single polymer is a novel approach to broadening vaccine coverage by eliminating the need for multiple polysaccharide sources to cover multiple serogroup members.

scholarly journals Complete Genome Sequence of Bordetella pertussis Pelita III, the Production Strain for an Indonesian Whole-Cell Pertussis Vaccine

2017 ◽  
Vol 5 (17) ◽  
Author(s):  
Yusuf Sofyan Efendi ◽  
Dwi Susanti ◽  
Erman Tritama ◽  
Michelle Lueders Pasier ◽  
Gilang Nadia Niwan Putri ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
World Health ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Whole Cell ◽  
Content Type ◽  
Health Organization ◽  
Production Strain

ABSTRACT PT Bio Farma, the sole World Health Organization-approved Indonesian vaccine producer, manufactures a whole-cell whooping cough vaccine (wP) that, as part of a pentavalent diphtheria-tetanus-pertussis/hepatitis B/Haemophilus influenzae b (DTP/HB/Hib) vaccine, is used in Indonesia and many other countries. We report here the whole-genome sequence for Bordetella pertussis Pelita III, PT Bio Farma’s wP production strain.

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