scholarly journals Role of Evolutionary Selection Acting on Vaccine Antigens in the Re-Emergence of Bordetella Pertussis

Diseases ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 35 ◽  
Author(s):  
Haley Etskovitz ◽  
Nicole Anastasio ◽  
Evangeline Green ◽  
Meghan May
Keyword(s):  
Bordetella Pertussis ◽  
Subunit Vaccine ◽  
Whooping Cough ◽  
Protein Secondary Structure ◽  
Purifying Selection ◽  
Evolutionary Selection ◽  
Diversifying Selection ◽  
Resistant Strains ◽  
Adhesin Proteins

Pertussis (“whooping cough”) is a re-emerging disease with increasing incidence among fully vaccinated individuals. We explored the genetic diversity of five Bordetella pertussis proteins used to generate the subunit vaccine across ancestral and newly emergent strains using immunoinformatics and evolutionary selection measurements. The five subunits of pertussis toxin (Ptx1–Ptx5) were highly conserved with regard to sequence, predicted structure, predicted antigenicity, and were under purifying selection. In contrast, the adhesin proteins pertactin (Prn) and filamentous hemagglutinin (FHA) were under statistically significant (p < 0.01) diversifying selection. Most heavily diversified sites of each protein fell within antigenic epitopes, and the functional adhesin motifs were conserved. Protein secondary structure was conserved despite sequence diversity for FHA but was changeable in Prn. These findings suggest that subunit vaccine-derived immunity does not impact Ptx1–Ptx5 but may apply evolutionary pressure to Prn and FHA to undergo diversifying selection. These findings offer further insight into the emergence of vaccine-resistant strains of B. pertussis.

scholarly journals Comparative Integrated Omics Analysis of the Hfq Regulon in Bordetella pertussis

2019 ◽  
Vol 20 (12) ◽  
pp. 3073 ◽  
Author(s):  
Ana Dienstbier ◽  
Fabian Amman ◽  
Daniel Štipl ◽  
Denisa Petráčková ◽  
Branislav Večerek
Keyword(s):  
Gene Expression ◽  
Bordetella Pertussis ◽  
Transcriptional Control ◽  
Whooping Cough ◽  
Expression Profiles ◽  
Bacterial Pathogen ◽  
Gene Expression Profiles ◽  
Control Of Gene Expression ◽  
Proteomic Data

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large number of genes are affected by the lack of Hfq. This study represents the first attempt to characterize the Hfq regulon in bacterial pathogen using an integrative omics approach. Gene expression profiles were analyzed by RNA-seq and protein amounts in cell-associated and cell-free fractions were determined by LC-MS/MS technique. Comparative analysis of transcriptomic and proteomic data revealed solid correlation (r2 = 0.4) considering the role of Hfq in post-transcriptional control of gene expression. Importantly, our study confirms and further enlightens the role of Hfq in pathogenicity of B. pertussis as it shows that Δhfq strain displays strongly impaired secretion of substrates of Type III secretion system (T3SS) and substantially reduced resistance to serum killing. On the other hand, significantly increased production of proteins implicated in transport of important metabolites and essential nutrients observed in the mutant seems to compensate for the physiological defect introduced by the deletion of the hfq gene.

scholarly journals Immunoglobulin A-Mediated Protection against Bordetella pertussis Infection

2001 ◽  
Vol 69 (8) ◽  
pp. 4846-4850 ◽  
Author(s):  
Sandra M. M. Hellwig ◽  
Annemiek B. van Spriel ◽  
Joop F. P. Schellekens ◽  
Frits R. Mooi ◽  
Jan G. J. van de Winkel
Keyword(s):  
Transgenic Mice ◽  
Bordetella Pertussis ◽  
Polymorphonuclear Leukocytes ◽  
Whooping Cough ◽  
Immunoglobulin A ◽  
Pertussis Infection ◽  
Bacterial Killing ◽  
Effector Functions ◽  
Human Polymorphonuclear Leukocytes

ABSTRACT Infection with Bordetella pertussis, the causative agent of pertussis (whooping cough) in humans, is followed by the production of antibodies of several isotypes, including immunoglobulin A (IgA). Little is known, however, about the role of IgA in immunity against pertussis. Therefore, we studied targeting ofB. pertussis to the myeloid receptor for IgA, FcαRI (CD89), using either IgA purified from immune sera of pertussis patients or bispecific antibodies directed against B. pertussis and FcαRI (CD89 BsAb). Both IgA and CD89 BsAb facilitated FcαRI-mediated binding, phagocytosis, and bacterial killing by human polymorphonuclear leukocytes (PMNL) and PMNL originating from human FcαRI-transgenic mice. Importantly, FcαRI targeting resulted in enhanced bacterial clearance in lungs of transgenic mice. These data support the capacity of IgA to induce anti-B. pertussis effector functions via the myeloid IgA receptor, FcαRI. Increasing the amount of IgA antibodies induced by pertussis vaccines may result in higher vaccine efficacy.

scholarly journals Eighty-Kilodalton N-Terminal Moiety of Bordetella pertussis Filamentous Hemagglutinin: Adherence, Immunogenicity, and Protective Role

2002 ◽  
Vol 70 (8) ◽  
pp. 4142-4147 ◽  
Author(s):  
Sylvie Alonso ◽  
Nathalie Reveneau ◽  
Kévin Pethe ◽  
Camille Locht
Keyword(s):  
Bordetella Pertussis ◽  
Protective Immunity ◽  
Whooping Cough ◽  
Protective Role ◽  
Wild Type ◽  
Functional Importance ◽  
Extracellular Milieu ◽  
Filamentous Hemagglutinin ◽  
Number Of Factors

ABSTRACT Bordetella pertussis, the etiological agent of whooping cough, produces a number of factors, such as toxins and adhesins, that are required for full expression of virulence. Filamentous hemagglutinin (FHA) is the major adhesin of B. pertussis. It is a protein of approximately 220 kDa, found both associated at the bacterial cell surface and secreted into the extracellular milieu. Despite its importance in B. pertussis pathogenesis and its inclusion in most acellular pertussis vaccines, little is known about the functional importance of individual domains in infection and in the induction of protective immunity. In this study, we analyzed the role of the approximately 80-kDa N-terminal domain of FHA, designated Fha44, in B. pertussis adherence, colonization, and immunogenicity. Although Fha44 contains the complete heparan sulfate-binding domain, it is not sufficient for adherence to epithelial cells or macrophages. It also cannot replace FHA during colonization of the mouse respiratory tract. Infection with a B. pertussis strain producing Fha44 instead of FHA does not induce anti-FHA antibodies, whereas such antibodies can readily be induced by intranasal administration of purified Fha44. In addition, mice immunized with purified Fha44 were protected against challenge with wild-type B. pertussis, indicating that Fha44 contains protective epitopes. Compared to FHA, Fha44 is much smaller and much more soluble and is therefore easier to purify and to store. These advantages may perhaps warrant considering Fha44 for inclusion in acellular pertussis vaccines.

scholarly journals Role of Immature Red Blood Cells in Neonatal Immunity

2019 ◽  
Vol 2 (2) ◽  
pp. 33-34
Author(s):  
Jappn Grewal ◽  
Lai Xu ◽  
Garett Dunsmore ◽  
Shokrollah Elahi
Keyword(s):  
Immune System ◽  
Red Blood Cells ◽  
Bordetella Pertussis ◽  
Blood Cells ◽  
Whooping Cough ◽  
Food Poisoning ◽  
Intracellular Bacteria ◽  
Older Children ◽  
Neonatal Immunity

Newborns are highly susceptible to diseases. Infections such as Bordetella Pertussis (i.e. whooping cough) and Listeria (i.e. food poisoning) can result in the death of neonates while causing little harm to older children and adults. Although previously attributed to an underdeveloped immune system, recent research has shown that this susceptibility is due to the high presence of immature red blood cells or CD71+ cells. These cells possess immunosuppressive properties. By interfering with the function of other immune cells, they can prevent an effective pathogenic immune response. In this study, the changes in the amount of CD71+ cells were observed throughout the different age points of mice as well as in mice infected with Bordetella pertussis and Listeria. This study aimed to gain a better understanding of the development of the immune system as to better aid neonates in fighting infection. Flow cytometry was used to determine the amount of CD71+ cells in the spleens of mice at different age points. The results showed that overall the amount of CD71+ cells decreased as the age of the mouse increased, paralleling the decrease in susceptibility of the immune system. Furthermore, the change in CD71+ cells was also observed in the spleens of mice infected with Bordetella pertussis and mice infected with Listeria. There was no significant change for the Listeria infected mice, as CD71+ cells play no immunological role in fighting Listeria, an intracellular bacteria. However, there was a significant increase in CD71+ cells in Bordetella Pertussis infected mice since this infection was extracellular. These results show that CD71+ cells react differently to different infections and play a different immunological role in the presence of different pathogens. Furthermore, the results shows a direct correlation between age and the amount of CD71+ cells present in the spleen. The changes in the amount of CD71+ cells was most likely due to different pathological conditions and requirements at different ages.

scholarly journals Strain-Dependent Role of BrkA during Bordetella pertussis Infection of the Murine Respiratory Tract

2004 ◽  
Vol 72 (10) ◽  
pp. 5919-5924 ◽  
Author(s):  
Kelly D. Elder ◽  
Eric T. Harvill
Keyword(s):  
Respiratory Tract ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Single Gene ◽  
Wild Type ◽  
Pertussis Infection ◽  
Redundant Functions

ABSTRACT Bordetella pertussis, the causative agent of whooping cough, expresses many virulence factors believed to be involved in infection and disease progression. While these factors as a group are required for infection, deletion of individual virulence factor genes generally has limited effects on the ability of B. pertussis to efficiently infect the respiratory tract of mice, suggesting they may perform noncritical or redundant functions. We have recently observed that a B. pertussis strain, putatively with a mutation of a single gene, brkA, results in a severe defect in vivo. Although BrkA has been shown to be required for B. pertussis to resist complement-mediated killing in vitro, the relevance of these findings to the in vivo role of BrkA during infection has not been examined. Transducing this mutation into multiple wild-type B. pertussis strains allowed us to confirm the in vitro phenotype of reduced resistance to serum complement. All ΔbrkA mutants were increased in their sensitivity to complement in vitro, both in the presence and absence of antibodies. However, these strains differed substantially in their phenotypes in vivo. ΔbrkA mutants of recent clinical isolates were indistinguishable from wild-type strains in their efficient infection of respiratory organs, suggesting that the function of BrkA in these strains is noncritical or redundant. In contrast, multiple ΔbrkA strains derived from Tohama I were severely defective during the first week postinoculation compared to their wild-type parent. This defect was present even in complement-deficient mice, revealing a complement-independent phenotype for the ΔbrkA mutant in respiratory tract infection.

scholarly journals Bordetella pertussis risA, but Not risS, Is Required for Maximal Expression of Bvg-Repressed Genes

2005 ◽  
Vol 73 (9) ◽  
pp. 5995-6004 ◽  
Author(s):  
Trevor H. Stenson ◽  
Andrew G. Allen ◽  
Jehan A. al-Meer ◽  
Duncan Maskell ◽  
Mark S. Peppler
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Cell Model ◽  
Regulatory System ◽  
Bacterial Invasion ◽  
Virulence Determinants ◽  
Heterologous System ◽  
Two Component ◽  
Maximal Expression

ABSTRACT Expression of virulence determinants by Bordetella pertussis, the primary etiological agent of whooping cough, is regulated by the BvgAS two-component regulatory system. The role of a second two-component regulatory system, encoded by risAS, in this process is not defined. Here, we show that mutation of B. pertussis risA does not affect Bvg-activated genes or proteins. However, mutation of risA resulted in greatly diminished expression of Bvg-repressed antigens and decreased transcription of Bvg-repressed genes. In contrast, mutation of risS had no effect on the expression of Bvg-regulated molecules. Mutation of risA also resulted in decreased bacterial invasion in a HeLa cell model. However, decreased invasion could not be attributed to the decreased expression of Bvg-repressed products, suggesting that mutation of risA may affect the expression of a variety of genes. Unlike the risAS operons in B. parapertussis and B. bronchiseptica, B. pertussis risS is a pseudogene that encodes a truncated RisS sensor. Deletion of the intact part of the B. pertussis risS gene does not affect the expression of risA-dependent, Bvg-repressed genes. These observations suggest that RisA activation occurs through cross-regulation by a heterologous system.

scholarly journals Structural and Technological Approach to Reveal the Role of the Lipid Phase in the Formation of Soy Emulsion Gels with Chia Oil

Gels ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 48
Author(s):  
Ana M. Herrero ◽  
Claudia Ruiz-Capillas
Keyword(s):  
Raman Spectroscopy ◽  
Structural Properties ◽  
Structural Changes ◽  
Protein Secondary Structure ◽  
Lipid Phase ◽  
Α Helix ◽  
Β Sheet ◽  
Shed Light ◽  
Chia Oil

Considerable attention has been paid to emulsion gels (EGs) in recent years due to their interesting applications in food. The aim of this work is to shed light on the role played by chia oil in the technological and structural properties of EGs made from soy protein isolates (SPI) and alginate. Two systems were studied: oil-free SPI gels (SPI/G) and the corresponding SPI EGs (SPI/EG) that contain chia oil. The proximate composition, technological properties (syneresis, pH, color and texture) and structural properties using Raman spectroscopy were determined for SPI/G and SPI/EG. No noticeable (p > 0.05) syneresis was observed in either sample. The pH values were similar (p > 0.05) for SPI/G and SPI/EG, but their texture and color differed significantly depending on the presence of chia oil. SPI/EG featured significantly lower redness and more lightness and yellowness and exhibited greater puncture and gel strengths than SPI/G. Raman spectroscopy revealed significant changes in the protein secondary structure, i.e., higher (p < 0.05) α-helix and lower (p < 0.05) β-sheet, turn and unordered structures, after the incorporation of chia oil to form the corresponding SPI/EG. Apparently, there is a correlation between these structural changes and the textural modifications observed.

scholarly journals Diphtheria-tetanus-pertussis vaccine combined with Bordetella parapertussis vaccine

1962 ◽  
Vol 60 (3) ◽  
pp. 289-293 ◽  
Author(s):  
Neda Köhler-Kubelka
Keyword(s):  
Clinical Examination ◽  
Pertussis Vaccine ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Production Test ◽  
Post Vaccination ◽  
Bordetella Parapertussis ◽  
Cross Reactions ◽  
Combined Vaccine

Investigations carried out to ascertain the ability of various strains of Bordetella pertussis and B. parapertussis to produce agglutinins have shown that the agglutinin response is considerably greater with B. parapertussis.Children inoculated with a combined vaccine in which the parapertussis element contained B. parapertussis in only one-twelfth of the concentration of B. pertussis in the pertussis element showed agglutinins in their sera in titres well above 1:300 for both organisms. There were no cross-reactions and the serological responses were specific throughout. The vaccine used was the standard diphtheria-tetanus-pertussis (DTP) prophylactic to which had been added a vaccine prepared from recently isolated strains of B. parapertussis.Agglutinin titres of both whooping cough components with the combined vaccine were somewhat lower in mice than was the case when monovalent vaccines were used, but they were considered to be satisfactory.It is suggested that the agglutination production test in mice could be used for the assessment of protective power of B. parapertussis vaccines against infection.I wish to thank Dr Ikić, director of the Institute of Immunology, Zagreb, who enabled me to perform all these examinations, further to Dr B. Mravunac and Dr Z. Radanov for having carried out vaccination in children and for the clinical examination of post vaccination reactions.

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.

Anti-Aging Effect of Siraitia grosuenorii by Enhancement of Hematopoietic Stem Cell Function

2016 ◽  
Vol 44 (04) ◽  
pp. 803-815 ◽  
Author(s):  
Lin Bai ◽  
Guiying Shi ◽  
Yajun Yang ◽  
Wei Chen ◽  
Lianfeng Zhang
Keyword(s):  
Aging Process ◽  
Cell Function ◽  
Whooping Cough ◽  
Aging Effect ◽  
Guangxi Province ◽  
Facs Analysis ◽  
Hematopoietic Stem ◽  
Associated Proteins

Anti-aging has always been a popular topic, and there are many claims about the existence of factors that can slow, stop, or even reverse the aging process. Siraitia grosuenorii, a local fruit in china, has been used for the treatment of gastritis, sore throats, and whooping cough in traditional Chinese medicine. The individuals who took the juice of Siraitia grosuenorii regularly had increased longevity in the Guangxi Province, which is located in the Southern part of China. In this paper, we fed mice with Siraitia grosuenorii for 10 months to identify the role of Siraitia grosuenorii in anti-aging and to investigate its corresponding mechanism. The results showed that mice fed with Siraitia grosuenorii displayed a slower aging process. The extension of the aging process was due to the enhanced function of HSCs. FACS analysis showed that the number of LSKs, LT-HSCs, ST-HSCs and MPPs from Siraitia grosuenorii mice was decreased. In vitro, a clonigenic assay showed that LT-HSCs from Siraitia grosuenorii mice increased the ability of self-renewal. Moreover, Siraitia grosuenorii mice maintained the quiescence of LSKs, decreased the level of ROS and reduced the amount of senescence associated β-gal positive cells. Furthermore, Siraitia grosuenorii mice decreased the expression of senescence-associated proteins. Siraitia grosuenorii maintained quiescence, decreased senescence and enhanced the function of HSCs, slowing the aging process of mice.

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