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5. Association between Fulminant Pertussis and Pertactin-Producing Bordetella Pertussis in Infants: A Multicenter Study in France, 2008-2019

Author

Pauline Leroux, Soraya Matczak, Bouchez Valérie, Antoine Ouziel, Elise Launay, Albert Faye, Valérie Rabier, Jean Sarlangue, Eric Jeziorski, Zoha Maakaroun-Vermesse, Fouad Madhi, Didier Pinquier, Mathie Lorrot, Marie Pouletty, Aymeric Cantais, Etienne Javouhey, Fatima Aït El Belghiti, Sophie Guillot, Carla Rodrigues, Sylvain Brisse, Jérémie F. Cohen, and Julie Toubiana

Published
2023

6. Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Author

Lefrancq, Noémie, primary, Bouchez, Valérie, additional, Fernandes, Nadia, additional, Barkoff, Alex-Mikael, additional, Bosch, Thijs, additional, Dalby, Tine, additional, Åkerlund, Thomas, additional, Darenberg, Jessica, additional, Fabianova, Katerina, additional, Vestrheim, Didrik F., additional, Fry, Norman K., additional, González-López, Juan José, additional, Gullsby, Karolina, additional, Habington, Adele, additional, He, Qiushui, additional, Litt, David, additional, Martini, Helena, additional, Piérard, Denis, additional, Stefanelli, Paola, additional, Stegger, Marc, additional, Zavadilova, Jana, additional, Armatys, Nathalie, additional, Landier, Annie, additional, Guillot, Sophie, additional, Hong, Samuel L., additional, Lemey, Philippe, additional, Parkhill, Julian, additional, Toubiana, Julie, additional, Cauchemez, Simon, additional, Salje, Henrik, additional, and Brisse, Sylvain, additional

Published
2022
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8. Genomic library of Bordetella

Author

Bridel, Sébastien, primary, Bouchez, Valérie, additional, Brancotte, Bryan, additional, Hauck, Sofia, additional, Armatys, Nathalie, additional, Landier, Annie, additional, Mühle, Estelle, additional, Guillot, Sophie, additional, Toubiana, Julie, additional, Maiden, Martin C.J., additional, Jolley, Keith A., additional, and Brisse, Sylvain, additional

Published
2022
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9. Evolution of Bordetella pertussis over a 23-year period in France, 1996 to 2018

Author

Bouchez, Valérie, Guillot, Sophie, Landier, Annie, Armatys, Nathalie, Matczak, Soraya, Toubiana, Julie, Brisse, Sylvain, Brieu, Nathalie, Hamdad, Farida, Kempf, Marie, Pailhoriès, Hélène, Jensen, Cécile, Lehours, Philippe, Guiraud, Jennifer, Le Bars, Hervé, Isnard, Christophe, Wilhelm, Nathalie, Le Coustumier, Alain, Delmas, Julien, De Briel, Dominique, Souply, Laurent, Aberrane, Saïd, Coudé, Marie, Garnier, Fabien, Descours, Ghislaine, Jean-Pierre, Hélène, Alauzet, Corentine, Gibaud, Sophie-Anne, Bonacorsi, Stéphane, Brasme, Lucien, Lemée, Ludovic, Koebel, Christelle, Lanotte, Philippe, Bland, Stéphane, Petitprez, Hélène, Raffenot, Didier, Levast, Marion, Doucet-Populaire, Florence, Bourgeois-Nicolaos, Nadège, Burucoa, Christophe, Grattard, Florence, Marque-Juillet, Stéphanie, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), This work was performed with the financial support of the Institut Pasteur and of Santé Publique France., French pertussis microbiology study group: Nathalie Brieu, Farida Hamdad, Marie Kempf, Hélène Pailhoriès, Cécile Jensen, Philippe Lehours, Jennifer Guiraud, Hervé Le Bars, Christophe Isnard, Nathalie Wilhelm, Alain Le Coustumier, Julien Delmas, Dominique De Briel, Laurent Souply, Saïd Aberrane, Marie Coudé, Fabien Garnier, Ghislaine Descours, Hélène Jean-Pierre, Corentine Alauzet, Sophie-Anne Gibaud, Stéphane Bonacorsi, Lucien Brasme, Ludovic Lemée, Christelle Koebel, Philippe Lanotte, Stéphane Bland, Hélène Petitprez, Didier Raffenot, Marion Levast, Florence Doucet-Populaire, Nadège Bourgeois-Nicolaos, Christophe Burucoa, Florence Grattard, Stéphanie Marque-Juillet, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Collège Doctoral, Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Institut Pasteur [Paris]

Subjects
Serotype, Bordetella pertussis, population evolution, Whooping Cough, Epidemiology, [SDV]Life Sciences [q-bio], Fimbria, MESH: Pertussis Toxin, MESH: Virulence Factors, Bordetella, Pertussis toxin, Microbiology, pertactin, MESH: Bordetella pertussis, 03 medical and health sciences, 0302 clinical medicine, Antigen, Virology, MESH: Child, medicine, Humans, Virulence Factors, Bordetella, 030212 general & internal medicine, Child, Whooping cough, 030304 developmental biology, Pertussis Vaccine, vaccine antigen deficiency, 0303 health sciences, Surveillance, MESH: Humans, biology, MESH: Bacterial Outer Membrane Proteins, Public Health, Environmental and Occupational Health, MESH: Whooping Cough, biology.organism_classification, medicine.disease, fimbriae serotype, 3. Good health, respiratory tract diseases, Vaccination, MESH: France, Pertussis Toxin, MESH: Pertussis Vaccine, France, Pertactin, Bacterial Outer Membrane Proteins
Abstract

Background Bordetella pertussis is the main agent of whooping cough. Vaccination with acellular pertussis vaccines has been largely implemented in high-income countries. These vaccines contain 1 to 5 antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and/or fimbrial proteins (FIM2 and FIM3). Monitoring the emergence of B. pertussis isolates that might partially escape vaccine-induced immunity is an essential component of public health strategies to control whooping cough. Aim We aimed to investigate temporal trends of fimbriae serotypes and vaccine antigen-expression in B. pertussis over a 23-year period in France (1996–2018). Methods Isolates (n = 2,280) were collected through hospital surveillance, capturing one third of hospitalised paediatric pertussis cases. We assayed PT, FHA and PRN production by Western blot (n = 1,428) and fimbriae production by serotyping (n = 1,058). Molecular events underlying antigen deficiency were investigated by genomic sequencing. Results The proportion of PRN-deficient B. pertussis isolates has increased steadily from 0% (0/38) in 2003 to 48.4% (31/64) in 2018 (chi-squared test for trend, p 481 insertion within the prn gene or a 22 kb genomic inversion involving the prn promoter sequence, indicative of convergent evolution. FIM2-expressing isolates have emerged since 2011 at the expense of FIM3. Conclusions B. pertussis is evolving through the rapid increase of PRN-deficient isolates and a recent shift from FIM3 to FIM2 expression. Excluding PRN, the loss of vaccine antigen expression by circulating B. pertussis isolates is epidemiologically insignificant.

Published
2021

10. Novel 1,3-dicarbonyl compounds having 2(3 H)-benzazolonic heterocycles as PPARγ agonists

Author

Blanc-Delmas, Elodie, Lebegue, Nicolas, Wallez, Valérie, Leclerc, Véronique, Yous, Saïd, Carato, Pascal, Farce, Amaury, Bennejean, Caroline, Renard, Pierre, Caignard, Daniel-Henri, Audinot-Bouchez, Valérie, Chomarat, Pascale, Boutin, Jean, Hennuyer, Nathalie, Louche, Katie, Carmona, Maria Carmen, Staels, Bart, Pénicaud, Luc, Casteilla, Louis, Lonchampt, Michel, Dacquet, Catherine, Chavatte, Philippe, Berthelot, Pascal, and Lesieur, Daniel

Published
2006
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15. Characterization of Post-Translational Modifications and Cytotoxic Properties of the Adenylate-Cyclase Hemolysin Produced by Various Bordetella pertussis and Bordetella parapertussis Isolates

Author

Bouchez, Valérie, Douché, Thibaut, Dazas, Mélody, Delaplane, Sophie, Matondo, Mariette, Chamot-Rooke, Julia, Guiso, Nicole, Prévention et Thérapie Moléculaires des Maladies humaines, Institut Pasteur [Paris] (IP), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Institut Pasteur Foundation and GlaxoSmithKline Biologicals, Rixensart, Belgium., We thank Nicolas Hegerle for his help at the start of this study., Institut Pasteur [Paris], and Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Bordetella parapertussis, PTMs, Macrophages, [SDV]Life Sciences [q-bio], lcsh:R, lcsh:Medicine, MESH: Adenylate Cyclase Toxin*/genetics, MESH: Macrophages/drug effects, MESH: Adenylate Cyclase Toxin*/metabolism, MESH: Bordetella parapertussis*/genetics, Article, Bordetella pertussis, Cell Line, MESH: Bordetella pertussis*/genetics, MESH: Cell Line, adenylate cyclase hemolysin, MESH: Bordetella parapertussis*/metabolism, MESH: Protein Processing, Post-Translational, Adenylate Cyclase Toxin, MESH: Bordetella pertussis*/metabolism, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein Processing, Post-Translational, MESH: Adenylate Cyclase Toxin*/toxicity
Abstract

International audience; Bordetella pertussis and Bordetella parapertussis are the causal agents of whooping cough in humans. They produce diverse virulence factors, including adenylate cyclase-hemolysin (AC-Hly), a secreted toxin of the repeat in toxins (RTX) family with cyclase, pore-forming, and hemolytic activities. Post-translational modifications (PTMs) are essential for the biological activities of the toxin produced by B. pertussis. In this study, we compared AC-Hly toxins from various clinical isolates of B. pertussis and B. parapertussis, focusing on (i) the genomic sequences of cyaA genes, (ii) the PTMs of partially purified AC-Hly, and (iii) the cytotoxic activity of the various AC-Hly toxins. The genes encoding the AC-Hly toxins of B. pertussis and B. parapertussis displayed very limited polymorphism in each species. Most of the sequence differences between the two species were found in the C-terminal part of the protein. Both toxins harbored PTMs, mostly corresponding to palmitoylations of the lysine 860 residue and palmoylations and myristoylations of lysine 983 for B. pertussis and AC-Hly and palmitoylations of lysine 894 and myristoylations of lysine 1017 for B. parapertussis AC-Hly. Purified AC-Hly from B. pertussis was cytotoxic to macrophages, whereas that from B. parapertussis was not.

Published
2017

22. Global Population Structure and Evolution of Bordetella pertussis and Their Relationship with Vaccination

Author

Bart, Marieke J., primary, Harris, Simon R., additional, Advani, Abdolreza, additional, Arakawa, Yoshichika, additional, Bottero, Daniela, additional, Bouchez, Valérie, additional, Cassiday, Pamela K., additional, Chiang, Chuen-Sheue, additional, Dalby, Tine, additional, Fry, Norman K., additional, Gaillard, María Emilia, additional, van Gent, Marjolein, additional, Guiso, Nicole, additional, Hallander, Hans O., additional, Harvill, Eric T., additional, He, Qiushui, additional, van der Heide, Han G. J., additional, Heuvelman, Kees, additional, Hozbor, Daniela F., additional, Kamachi, Kazunari, additional, Karataev, Gennady I., additional, Lan, Ruiting, additional, Lutyńska, Anna, additional, Maharjan, Ram P., additional, Mertsola, Jussi, additional, Miyamura, Tatsuo, additional, Octavia, Sophie, additional, Preston, Andrew, additional, Quail, Michael A., additional, Sintchenko, Vitali, additional, Stefanelli, Paola, additional, Tondella, M. Lucia, additional, Tsang, Raymond S. W., additional, Xu, Yinghua, additional, Yao, Shu-Man, additional, Zhang, Shumin, additional, Parkhill, Julian, additional, and Mooi, Frits R., additional

Published
2014
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26. Effect of Oxime Ether Incorporation in Acyl Indole Derivatives on PPAR Subtype Selectivity

Author

Le Naour, Morgan, primary, Leclerc, Veronique, additional, Farce, Amaury, additional, Caignard, Daniel‐Henri, additional, Hennuyer, Nathalie, additional, Staels, Bart, additional, Audinot‐Bouchez, Valérie, additional, Boutin, Jean‐Albert, additional, Lonchampt, Michel, additional, Dacquet, Catherine, additional, Ktorza, Alain, additional, Berthelot, Pascal, additional, and Lebegue, Nicolas, additional

Published
2012
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30. Novel 1,3-dicarbonyl compounds having 2(3H)-benzazolonic heterocycles as PPARγ agonists

Author

Blanc-Delmas, Elodie, primary, Lebegue, Nicolas, additional, Wallez, Valérie, additional, Leclerc, Véronique, additional, Yous, Saïd, additional, Carato, Pascal, additional, Farce, Amaury, additional, Bennejean, Caroline, additional, Renard, Pierre, additional, Caignard, Daniel-Henri, additional, Audinot-Bouchez, Valérie, additional, Chomarat, Pascale, additional, Boutin, Jean, additional, Hennuyer, Nathalie, additional, Louche, Katie, additional, Carmona, Maria Carmen, additional, Staels, Bart, additional, Pénicaud, Luc, additional, Casteilla, Louis, additional, Lonchampt, Michel, additional, Dacquet, Catherine, additional, Chavatte, Philippe, additional, Berthelot, Pascal, additional, and Lesieur, Daniel, additional

Published
2006
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34. Global Population Structure and Evolution of Bordetella pertussisand Their Relationship with Vaccination

Author

Bart, Marieke J., Harris, Simon R., Advani, Abdolreza, Arakawa, Yoshichika, Bottero, Daniela, Bouchez, Valérie, Cassiday, Pamela K., Chiang, Chuen-Sheue, Dalby, Tine, Fry, Norman K., Gaillard, María Emilia, van Gent, Marjolein, Guiso, Nicole, Hallander, Hans O., Harvill, Eric T., He, Qiushui, van der Heide, Han G. J., Heuvelman, Kees, Hozbor, Daniela F., Kamachi, Kazunari, Karataev, Gennady I., Lan, Ruiting, Lutyńska, Anna, Maharjan, Ram P., Mertsola, Jussi, Miyamura, Tatsuo, Octavia, Sophie, Preston, Andrew, Quail, Michael A., Sintchenko, Vitali, Stefanelli, Paola, Tondella, M. Lucia, Tsang, Raymond S. W., Xu, Yinghua, Yao, Shu-Man, Zhang, Shumin, Parkhill, Julian, and Mooi, Frits R.

Abstract

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 343 B. 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 which B. 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 by Bordetella 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 343 B. 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 of B. pertussisis evolving in response to vaccine introduction, potentially enabling vaccine escape.

Published
2014
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35. Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis

Author

Noémie Lefrancq, Valérie Bouchez, Nadia Fernandes, Alex-Mikael Barkoff, Thijs Bosch, Tine Dalby, Thomas Åkerlund, Jessica Darenberg, Katerina Fabianova, Didrik F. Vestrheim, Norman K. Fry, Juan José González-López, Karolina Gullsby, Adele Habington, Qiushui He, David Litt, Helena Martini, Denis Piérard, Paola Stefanelli, Marc Stegger, Jana Zavadilova, Nathalie Armatys, Annie Landier, Sophie Guillot, Samuel L. Hong, Philippe Lemey, Julian Parkhill, Julie Toubiana, Simon Cauchemez, Henrik Salje, Sylvain Brisse, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Cambridge [UK] (CAM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), University of Turku, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Statens Serum Institut [Copenhagen], The Public Health Agency of Sweden, National Institute of Public Health [Prague], Norwegian Institute of Public Health [Oslo] (NIPH), Public Health England [London], Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Uppsala University, Children's Health Ireland [Crumlin, Dublin, Ireland] (CHI), Vrije Universiteit Brussel (VUB), Istituto Superiore di Sanità (ISS), Rega Institute, Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The study was supported financially by the French Government Investissement d’Avenir grant ANR-16-CONV-0005 (INCEPTION project, to S.B. and H.S.). The National Reference Center for Whooping Cough and Other Bordetella Infections receives support from Institut Pasteur and Public Health France (Santé publique France, Saint Maurice, France). This work was also supported financially by the French Government’s Investissement d’Avenir program Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) to S.B. and a European Research Council (no. 804744 to H.S.). P.L. acknowledges funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725422-ReservoirDOCS)., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 804744,H2020-EU.1.1.,ARBODYNAMIC(2019), European Project: 725422,ERC-2016-COG,ReservoirDOCS(2017), Supporting clinical sciences, Microbiology and Infection Control, Clinical Biology, Lefrancq, Noémie [0000-0001-5991-6169], Bouchez, Valérie [0000-0002-5947-6383], Fernandes, Nadia [0000-0003-4595-9939], Dalby, Tine [0000-0003-4774-7091], Åkerlund, Thomas [0000-0001-7516-0218], Darenberg, Jessica [0000-0002-8528-8570], Fabianova, Katerina [0000-0001-8374-4395], Fry, Norman K [0000-0003-4862-6507], González-López, Juan José [0000-0003-2419-5909], Gullsby, Karolina [0000-0002-9673-0483], Habington, Adele [0000-0001-6997-3327], Litt, David [0000-0002-9215-0553], Martini, Helena [0000-0002-5877-9948], Piérard, Denis [0000-0002-7756-3691], Stefanelli, Paola [0000-0003-1620-4385], Stegger, Marc [0000-0003-0321-1180], Armatys, Nathalie [0000-0003-2042-4241], Landier, Annie [0000-0002-8278-4026], Hong, Samuel L [0000-0001-6354-4943], Lemey, Philippe [0000-0003-2826-5353], Parkhill, Julian [0000-0002-7069-5958], Cauchemez, Simon [0000-0001-9186-4549], Salje, Henrik [0000-0003-3626-4254], Brisse, Sylvain [0000-0002-2516-2108], and Apollo - University of Cambridge Repository

Subjects
Europe, Pertussis Vaccine, Genotype, Whooping Cough, [SDV]Life Sciences [q-bio], Humans, General Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bordetella pertussis
Abstract

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.

Published
2022
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36. Resurgence of Bordetella pertussis , including one macrolide-resistant isolate, France, 2024.

Author

Rodrigues C, Bouchez V, Soares A, Trombert-Paolantoni S, Aït El Belghiti F, Cohen JF, Armatys N, Landier A, Blanchot T, Hervo M, Toubiana J, and Brisse S

Subjects
Humans, France epidemiology, Drug Resistance, Bacterial, Microbial Sensitivity Tests, Bacterial Outer Membrane Proteins genetics, Whole Genome Sequencing, Virulence Factors, Bordetella genetics, Genotype, Adult, Child, Incidence, Child, Preschool, Bordetella pertussis genetics, Bordetella pertussis isolation & purification, Bordetella pertussis drug effects, Macrolides pharmacology, Whooping Cough epidemiology, Whooping Cough microbiology, Anti-Bacterial Agents pharmacology
Abstract

As other European countries, France is experiencing a resurgence of pertussis in 2024. Between 1 January and 31 May 2024, 5,616 (24.9%) positive Bordetella pertussis qPCR tests were identified, following a 3-year period of almost null incidence. Of 67 cultured and whole genome sequenced B. pertussis isolates, 66 produced pertactin and 56 produced FIM2, in contrast to pre-COVID-19 years. One isolate of genotype Bp-AgST4 was resistant to macrolides. Pertussis resurgence may favour isolates that produce FIM2 and pertactin.

Published
2024
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37. Transient reemergence of Bordetella parapertussis in France in 2022.

Author

Bouchez V, Toubiana J, Guillot S, Parapertussis Study Group, El Belghiti FA, Landier A, Armatys N, Trombert-Paolantoni S, Soares A, Rodrigues C, and Brisse S

Subjects
France epidemiology, Humans, Real-Time Polymerase Chain Reaction, Bacterial Outer Membrane Proteins genetics, Bordetella Infections microbiology, Bordetella Infections epidemiology, Child, Child, Preschool, Adult, Virulence Factors, Bordetella genetics, Female, COVID-19 epidemiology, Adolescent, Infant, Male, Young Adult, Bordetella parapertussis genetics, Bordetella parapertussis isolation & purification, Whooping Cough epidemiology, Whooping Cough microbiology
Abstract

Between March and October 2022, a peak of detection of Bordetella parapertussis by qPCR, real-time PCR was observed in France. Hypothesis/Gap Statement. Whether this peak was due to resurgence from previous circulating lineages or reintroduction into the country was unknown. Objective. The objective of this study is to understand B. parapertussis- transient increase observed in France in 2022 whereas it had virtually stopped being reported since the start of the COVID-19 pandemic in 2020. Methods. We analysed real-time PCR (qPCR) data from the two largest French outpatient laboratories performing whooping cough diagnosis and characterized all B. parapertussis isolates collected in the 2016-2022 period by the French National Reference Centre for Whooping Cough. Results. Microbiological analyses reveal that 13 of 18 bacterial isolates collected in 2022 produce the vaccine antigen pertactin, whereas none of the 22 isolates collected in the 2016-2021 period did. Conclusion. We hypothesize a re-introduction of B. parapertussis from regions of the world where whole-cell vaccines are still in use.

Published
2024
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38. Evolution of Bordetella pertussis over a 23-year period in France, 1996 to 2018.

Author

Bouchez V, Guillot S, Landier A, Armatys N, Matczak S, Toubiana J, and Brisse S

Subjects
Bacterial Outer Membrane Proteins genetics, Child, France epidemiology, Humans, Pertussis Toxin, Pertussis Vaccine, Virulence Factors, Bordetella genetics, Bordetella pertussis genetics, Whooping Cough epidemiology, Whooping Cough prevention & control
Abstract

Background Bordetella pertussis is the main agent of whooping cough. Vaccination with acellular pertussis vaccines has been largely implemented in high-income countries. These vaccines contain 1 to 5 antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and/or fimbrial proteins (FIM2 and FIM3). Monitoring the emergence of B. pertussis isolates that might partially escape vaccine-induced immunity is an essential component of public health strategies to control whooping cough.AimWe aimed to investigate temporal trends of fimbriae serotypes and vaccine antigen-expression in B. pertussis over a 23-year period in France (1996-2018).MethodsIsolates (n = 2,280) were collected through hospital surveillance, capturing one third of hospitalised paediatric pertussis cases. We assayed PT, FHA and PRN production by Western blot (n = 1,428) and fimbriae production by serotyping (n = 1,058). Molecular events underlying antigen deficiency were investigated by genomic sequencing.ResultsThe proportion of PRN-deficient B. pertussis isolates has increased steadily from 0% (0/38) in 2003 to 48.4% (31/64) in 2018 (chi-squared test for trend, p < 0.0001), whereas only 5 PT-, 5 FHA- and 9 FIM-deficient isolates were found. Impairment of PRN production was predominantly due to IS 481 insertion within the prn gene or a 22 kb genomic inversion involving the prn promoter sequence, indicative of convergent evolution. FIM2-expressing isolates have emerged since 2011 at the expense of FIM3.Conclusions B. pertussis is evolving through the rapid increase of PRN-deficient isolates and a recent shift from FIM3 to FIM2 expression. Excluding PRN, the loss of vaccine antigen expression by circulating B. pertussis isolates is epidemiologically insignificant.

Published
2021
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39. Characterization of Post-Translational Modifications and Cytotoxic Properties of the Adenylate-Cyclase Hemolysin Produced by Various Bordetella pertussis and Bordetella parapertussis Isolates.

Author

Bouchez V, Douché T, Dazas M, Delaplane S, Matondo M, Chamot-Rooke J, and Guiso N

Subjects
Cell Line, Macrophages drug effects, Protein Processing, Post-Translational, Adenylate Cyclase Toxin genetics, Adenylate Cyclase Toxin metabolism, Adenylate Cyclase Toxin toxicity, Bordetella parapertussis genetics, Bordetella parapertussis metabolism, Bordetella pertussis genetics, Bordetella pertussis metabolism
Abstract

Bordetella pertussis and Bordetella parapertussis are the causal agents of whooping cough in humans. They produce diverse virulence factors, including adenylate cyclase-hemolysin (AC-Hly), a secreted toxin of the repeat in toxins (RTX) family with cyclase, pore-forming, and hemolytic activities. Post-translational modifications (PTMs) are essential for the biological activities of the toxin produced by B. pertussis . In this study, we compared AC-Hly toxins from various clinical isolates of B. pertussis and B. parapertussis , focusing on (i) the genomic sequences of cyaA genes, (ii) the PTMs of partially purified AC-Hly, and (iii) the cytotoxic activity of the various AC-Hly toxins. The genes encoding the AC-Hly toxins of B. pertussis and B. parapertussis displayed very limited polymorphism in each species. Most of the sequence differences between the two species were found in the C-terminal part of the protein. Both toxins harbored PTMs, mostly corresponding to palmitoylations of the lysine 860 residue and palmoylations and myristoylations of lysine 983 for B. pertussis and AC-Hly and palmitoylations of lysine 894 and myristoylations of lysine 1017 for B. parapertussis AC-Hly. Purified AC-Hly from B. pertussis was cytotoxic to macrophages, whereas that from B. parapertussis was not.

Published
2017
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