The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice

Romero, Rodrigo Villarino; Bibova, Ilona; Černý, Ondřej; Večerek, Branislav; Wald, Tomáš; Benada, Oldřich; Zavadilová, Jana; Osička, Radim; Šebo, Peter

doi:10.1128/iai.02017-14

Cited by 2 publications

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“…Since then, both passive immunization with anti-CyaA antibodies, as well as active immunization with CyaA-derived material purified from B. pertussis, and in particular with the more homogeneous and LPS-free AC -toxoid preparations purified from recombinant E. coli, were shown to confer on mice a high level of protection against a respiratory challenge by B. pertussis [18,20,22,[79][80][81][82].…”

Section: Immunogenicity In Bordetella Infections and Protective Antigenmentioning

confidence: 98%

“…Among the advantages of this approach is the long-term stability of the purified denatured CyaA in 8 M urea solutions that can be frozen or lyophilized for long-term storage. Highly biologically active and/or antigenic CyaA is obtained by simple dilution of concentrated CyaA stocks over 100-fold into calcium-containing buffer lacking urea, or even with physiological saline [18,20,22,[79][80][81][82].…”

Section: Production Possibilities Process and Formulation Issuesmentioning

confidence: 99%

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Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

Šebo¹,

Osička

Mašín

2014

Expert Review of Vaccines

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The adenylate cyclase toxin-hemolysin (ACT, AC-Hly or CyaA) is a key virulence factor of Bordetella pertussis. It targets bactericidal activities of phagocytes, such as oxidative burst and complement- or antibody-mediated opsonophagocytic killing of bacteria. Through cAMP signaling, CyaA also skews TLR-triggered maturation of dendritic cells, inhibiting proinflammatory IL-12 and TNF-α secretion and enhancing IL-10 production and Treg expansion, likely hampering induction of adaptive immune responses to Bordetella infections. Non-enzymatic CyaA toxoid is a potent protective antigen and adjuvant that boosts immunogenicity of co-administered B. pertussis antigens and improves potency of acellular pertussis (aP) vaccines in mice. This makes CyaA a prime antigen candidate for inclusion into a next generation of aP vaccines. Moreover, recombinant CyaA toxoids were recently shown to be safe in humans in frame of Phase I clinical evaluation of a CyaA-based immunotherapeutic vaccine that induces Th1-polarized CD8(+) cytotoxic T-lymphocyte responses targeting cervical tumors.

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Section: Immunogenicity In Bordetella Infections and Protective Antigenmentioning

confidence: 98%

Section: Production Possibilities Process and Formulation Issuesmentioning

confidence: 99%

Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

Šebo¹,

Osička

Mašín

2014

Expert Review of Vaccines

Self Cite

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“…Moreover, while immunization of mice with Bsp22 does not confer protection against an intranasal challenge with B. pertussis, it does lead to a significant reduction in colonization by B. bronchiseptica [21,25].…”

Section: Introductionmentioning

confidence: 97%

Bsp22 protein polymerization drives dynamic adaptation of theBordetellatype III secretion system injectisome

Malcova,

Kamanova

2024

Preprint

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Many gram-negative bacteria are equipped with a type III secretion system (T3SS) injectisome, enabling the direct translocation of effector proteins from the bacterial cytoplasm into host cells. In the case of Bordetella bronchiseptica, a respiratory pathogen of diverse mammals, the T3SS injectisome exhibits a unique needle tip filament formed by the Bsp22 protein, essential for bacterial persistence in mice. Here, we used B. bronchiseptica and B.pertussis with in-frame insertions of short peptide tags into the Bsp22 to elucidate its formation and characteristics via super-resolution imaging with fluorophore-labeled nanobodies and biarsenic probes. We report that on abiotic surfaces, Bsp22 forms flexible filaments that protrude up to several um from bacterial cells. In these conditions, Bsp22 filaments grow continuously without any apparent growth control, with Bsp22 subunits being added at the distal end. Remarkably, during host cell infection, the growth of Bsp22 filaments is constrained, accompanied by downregulated Bsp22 protein production. When infecting HeLa cells, some Bsp22 filaments form a short physical bridge between the bacterium and the host cell surface. In nasal epithelium, where B. bronchiseptica colonization is specifically restricted to ciliated cells, Bsp22 filaments align parallel to the cilia, pointing towards the cell apical surface. These results highlight the context-specific and environment-influenced dynamic modulation of the length and orientation of Bordetella needle tip filament, uncovering the adaptability of the Bordetella T3SS injectisome in response to conditions encountered during host cell infection.

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The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice

Cited by 2 publications

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Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

Bsp22 protein polymerization drives dynamic adaptation of theBordetellatype III secretion system injectisome

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