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

Valerie Bouchez (1) , Thibaut Douche (2) , Mélody Dazas (1) , Sophie Delaplane (1) , Mariette Matondo (2) , Julia Chamot-Rooke (2) , Nicole Guiso (1)

1 Prévention et Thérapie Moléculaires des Maladies humaines
2 UTechS MSBio - Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology

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.

Mots clés: Bordetella parapertussis; Bordetella pertussis; PTMs; adenylate cyclase hemolysin

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire

Valerie Bouchez, Thibaut Douche, Mélody Dazas, Sophie Delaplane, Mariette Matondo, et al.. Characterization of Post-Translational Modifications and Cytotoxic Properties of the Adenylate-Cyclase Hemolysin Produced by Various Bordetella pertussis and Bordetella parapertussis Isolates. Toxins, 2017, 9 (10), pp.304. ⟨10.3390/toxins9100304⟩. ⟨pasteur-02573143⟩