Article
Immunology
Giusto D. Badami, Marco P. La Manna, Paola Di Carlo, Ondrej Stanek, Irena Linhartova, Nadia Caccamo, Peter Sebo, Francesco Dieli
Summary: HLA-E-restricted CD8+ T lymphocytes play a critical role in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. This study investigates the ability of the enzymatically inactive Bordetella pertussis adenylate cyclase (CyaA) toxoid to deliver HLA-E-binding Mtb epitopes for expanding human CD8+ T cells in vitro. The results demonstrate that the CyaA-toxoid containing HLA-E-restricted Mtb epitopes can significantly expand antigen-specific CD8+ T cells and promote interferon-gamma production and cytotoxic activity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna Malandra, Waheed Ur Rahman, Nela Klimova, Gaia Streparola, Jana Holubova, Adriana Osickova, Simone Bariselli, Peter Sebo, Radim Osicka
Summary: Research shows that Bordetella pertussis toxins CyaA and PT can induce the production of major airway mucins in infected airway epithelial cells by activating the cAMP response element binding protein (CREB). Mutant strains of B. pertussis that can only secrete active PT or produce enzymatically inactive CyaA-AC(-) toxoid fail to trigger significant mucus production, while strains secreting active CyaA toxin and PT toxoid can elicit mucin production efficiently.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Maryam Golshani, Waheed Ur Rahman, Adriana Osickova, Jana Holubova, Jinery Lora, Nataliya Balashova, Peter Sebo, Radim Osicka
Summary: The pertussis agent Bordetella pertussis produces a virulence factor called filamentous hemagglutinin (FhaB) that plays a crucial role in adhesion and infection. FhaB protein translocates through an FhaC pore to the outer bacterial surface and is then processed to a smaller fragment. Contrary to previous suggestions, the study found that FhaB does not bind the beta(2) integrin CD11b/CD18 but instead interacts with sulfated glycosaminoglycans on the cell surface.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Michal Cesnek, Michal Safranek, Martin Dracinsky, Eva Tloust'ova, Helena Mertlikova-Kaiserova, Michael P. Hayes, Val J. Watts, Zlatko Janeba
Summary: A series of potent acyclic nucleoside phosphonates (ANPs) were designed as inhibitors of bacterial ACs, showing substantial selectivity and significant inhibitory effects in cell-based and cell-free assays. These compounds represent the most effective ACT/EF inhibitors based on ANPs reported to date.
Article
Food Science & Technology
Marilyne Davi, Mirko Sadi, Irene Pitard, Alexandre Chenal, Daniel Ladant
Summary: Various bacterial pathogens are producing toxins that target the cyclic Nucleotide Monophosphate (cNMPs) signaling pathways in order to facilitate host colonization. Here we describe a simple and robust in vitro assay for AC activity based on the spectrophotometric detection of cyclic AMP (cAMP) after chromatographic separation on aluminum oxide.
Article
Chemistry, Multidisciplinary
Alexis Voegele, Mirko Sadi, Darragh Patrick O'Brien, Pauline Gehan, Dorothee Raoux-Barbot, Maryline Davi, Sylviane Hoos, Sebastien Brule, Bertrand Raynal, Patrick Weber, Ariel Mechaly, Ahmed Haouz, Nicolas Rodriguez, Patrice Vachette, Dominique Durand, Sebastien Brier, Daniel Ladant, Alexandre Chenal
Summary: The P454 segment of the CyaA toxin is capable of translocating across membranes and interacting with calmodulin, with key residues involved in membrane destabilization and calmodulin binding. Inhibitors of calmodulin can efficiently block CyaA internalization. This suggests a potential mechanism for the vectorial translocation of the toxin into host cells.
Article
Food Science & Technology
Lisa Szymkowicz, Jeffery Gerard, Benjamin Messham, Wai Wan Vivian Tam, D. Andrew James
Summary: This paper describes an LC-MS method for simultaneous analysis of residual protein toxins and small molecule glycopeptides in Pertussis toxin vaccine antigens. While ACT and TCT are quantified using MRM, DNT is currently monitored through animal testing, and new approaches for DNT testing are discussed.
Review
Food Science & Technology
Daniel Ladant
Summary: The adenylate cyclase toxin CyaA is a key virulent factor produced by Bordetella pertussis, targeting innate immunity to facilitate bacterial colonization of the respiratory tract. With remarkable characteristics, CyaA has been utilized for various applications in vaccinology and biotechnology. Its engineering as a vaccine vehicle for antigen delivery and as a genetic assay for monitoring protein-protein interactions in bacteria are briefly summarized in this chapter.
Article
Biochemistry & Molecular Biology
Jana Holubova, Attila Juhasz, Jiri Masin, Ondrej Stanek, David Jurnecka, Adriana Osickova, Peter Sebo, Radim Osicka
Summary: The whooping cough agent, Bordetella pertussis, secretes a toxin-hemolysin that affects host cells by increasing cAMP levels and forming pores, however, enhancing or reducing the pore-forming activity does not significantly alter its virulence in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Food Science & Technology
Camille Locht
Summary: This article summarizes the main contributions of scientists from Pasteur Institutes to the current knowledge of toxins produced by Bordetella pertussis. It highlights the identification of B. pertussis as the causative agent of whooping cough and the significant contributions made by Pasteurians in understanding the structure-function relationship of key toxins. It also discusses the potential applications of this knowledge in various fields, including protein-protein interaction studies, antigen delivery tools, and vaccine development.
Article
Immunology
Mariela del Carmen Carrica, Juan Pablo Gorgojo, Yanina Andrea Lamberti, Hugo Alberto Valdez, Maria Eugenia Rodriguez
Summary: B. parapertussis CyaA intoxicates human macrophages, prevents bacterial phagocytosis, and hinders phago-lysosomal fusion, promoting bacterial survival. CyaA also causes downregulation of host genes involved in antimicrobial defense and pro-inflammatory response, while upregulating anti-inflammatory cytokine IL-10. CyaA plays a central role in immune evasion and persistence of B. parapertussis.
MICROBIAL PATHOGENESIS
(2023)
Article
Immunology
Rinu Sivarajan, David Komla Kessie, Heike Oberwinkler, Niklas Pallmann, Thorsten Walles, Agmal Scherzad, Stephan Hackenberg, Maria Steinke
Summary: The study created three-dimensional tissue models of human ciliated nasal and tracheo-bronchial mucosa, investigating the response towards the B. pertussis virulence factor CyaA. The nasal tissue models exhibited an increased innate immune response compared to tracheo-bronchial tissue models, potentially reflecting the key role of nasal airway mucosa as the primary defense against airborne pathogens.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Jan Capek, Ilona Prochazkova, Tomas Matousek, David Hot, Branislav Vecerek
Summary: The human-restricted pathogen Bordetella pertussis has evolved a unique reverse adaptation mechanism through an inhibitory duplication within a manganese exporter gene, allowing it to accumulate manganese and improve survival under stress conditions. This specialized process assists B. pertussis in adjusting to environments with varying levels of manganese, enhancing its resistance to both toxicity and scarcity of the nutrient.
Article
Immunology
Jakub Drzmisek, Denisa Petrackova, Ana Dienstbier, Ivana Curnova, Branislav Vecerek
Summary: Bordetella pertussis produces the type III secretion system, and the novel chaperone BP2265 interacts specifically with the secreted T3SS regulator BtrA. In the absence of BP2265, secretion of BtrA and most T3SS substrates is severely impaired, while their production remains unaffected.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Microbiology
Audra R. Fullen, Jessica L. Gutierrez-Ferman, Rachael E. Rayner, Sun Hee Kim, Phylip Chen, Purnima Dubey, Daniel J. Wozniak, Mark E. Peeples, Estelle Cormet-Boyaka, Rajendar Deora
Summary: This study found that the pertussis pathogen Bordetella pertussis (Bp) can form aggregates, clusters, and highly structured biofilms on human bronchial epithelial cells. The biofilms consist of Bps polysaccharides, extracellular DNA, and bacterial cells. The study also revealed the positive roles of Bps, filamentous hemagglutinin, and adenylate cyclase toxin in biofilm formation.