N. H. Carbonetti, Pertussis toxin and adenylate cyclase toxin: Key virulence factors of Bordetella pertussis and cell biology tools, Future Microbiol, vol.5, pp.455-469, 2010.

J. A. Melvin, E. V. Scheller, J. F. Miller, and P. A. Cotter, Bordetella pertussis pathogenesis: Current and future challenges, Nat. Rev. Microbiol, vol.12, pp.274-288, 2014.

N. Guiso, Bordetella Adenylate Cyclase-Hemolysin Toxins, Toxins, vol.9, p.277, 2017.

J. Vojtova, J. Kamanova, and P. Sebo, Bordetella adenylate cyclase toxin: A swift saboteur of host defense, Curr. Opin. Microbiol, vol.9, pp.69-75, 2006.

H. Ostolaza, C. Martin, D. Gonzalez-bullon, K. B. Uribe, and A. Etxaniz, Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes, vol.9, p.295, 2017.

D. Ladant and A. Ullmann, Bordetella pertussis adenylate cyclase: A toxin with multiple talents, Trends Microbiol, vol.7, pp.172-176, 1999.

M. Simsova, G. Karimova, P. Sebo, and D. Ladant, Biotechnological applications of the Bordetella pertussis adenylate cyclase toxin, Bordetella pertussis Molecular Microbiology

C. Locht and . Ed, , pp.209-243, 2007.

G. Moron, G. Dadaglio, and C. Leclerc, New tools for antigen delivery to the MHC class I pathway, Trends Immunol, vol.25, pp.92-97, 2004.

M. El-azami-el-idrissi, D. Ladant, and C. Leclerc, The adenylate cyclase of Bordetella pertussis: A vector to target antigen presenting cells, Toxicon Off. J. Int. Soc. Toxinology, vol.40, pp.1661-1665, 2002.

A. A. Weiss, E. L. Hewlett, G. A. Myers, and S. Falkow, Pertussis toxin and extracytoplasmic adenylate cyclase as virulence factors of Bordetella pertussis, J. Infect. Dis, vol.150, pp.219-222, 1984.

A. A. Weiss and M. S. Goodwin, Lethal infection by Bordetella pertussis mutants in the infant mouse model, Infect. Immun, vol.57, pp.3757-3764, 1989.

N. Guiso, M. Rocancourt, M. Szatanik, and J. M. Alonso, Bordetella adenylate cyclase is a virulence associated factor and an immunoprotective antigen, Microb. Pathog, vol.7, pp.373-380, 1989.

E. T. Harvill, P. A. Cotter, M. H. Yuk, and J. F. Miller, Probing the function of Bordetella bronchiseptica adenylate cyclase toxin by manipulating host immunity, Infect. Immun, vol.67, pp.1493-1500, 1999.

D. L. Confer and J. W. Eaton, Phagocyte impotence caused by an invasive bacterial adenylate cyclase, Science, vol.217, pp.948-950, 1982.

N. Khelef, A. Zychlinsky, and N. Guiso, Bordetella pertussis induces apoptosis in macrophages: Role of adenylate cyclase-hemolysin, Infect. Immun, vol.61, pp.4064-4071, 1993.

P. Guermonprez, N. Khelef, E. Blouin, P. Rieu, P. Ricciardi-castagnoli et al., The adenylate cyclase toxin of Bordetella pertussis binds to target cells via the alpha(M)beta(2) integrin (CD11b/CD18), J. Exp. Med, vol.193, pp.1035-1044, 2001.

M. El-azami-el-idrissi, C. Bauche, J. Loucka, R. Osicka, P. Sebo et al., Interaction of Bordetella pertussis adenylate cyclase with CD11b/CD18: Role of toxin acylation and identification of the main integrin interaction domain, J. Biol. Chem, vol.278, pp.38514-38521, 2003.

D. J. Perkins, M. C. Gray, E. L. Hewlett, and S. N. Vogel, Bordetella pertussis adenylate cyclase toxin (ACT) induces cyclooxygenase-2 (COX-2) in murine macrophages and is facilitated by ACT interaction with CD11b/CD18 (Mac-1), Mol. Microbiol, vol.66, pp.1003-1015, 2007.

J. C. Eby, C. L. Hoffman, L. A. Gonyar, and E. L. Hewlett, Review of the neutrophil response to Bordetella pertussis infection, Pathog. Dis, vol.73, p.81, 2015.

J. Kamanova, O. Kofronova, J. Masin, H. Genth, J. Vojtova et al., Adenylate cyclase toxin subverts phagocyte function by RhoA inhibition and unproductive ruffling, J. Immunol. Baltim. Md, vol.181, pp.5587-5597, 1950.

O. Cerny, J. Kamanova, J. Masin, I. Bibova, K. Skopova et al., Bordetella pertussis Adenylate Cyclase Toxin Blocks Induction of Bactericidal Nitric Oxide in Macrophages through cAMP-Dependent Activation of the SHP-1 Phosphatase, J. Immunol. Baltim. Md, vol.194, pp.4901-4913, 1950.

O. Cerny, K. E. Anderson, L. R. Stephens, P. T. Hawkins, P. Sebo et al., Signaling of Adenylate Cyclase Toxin Blocks the Oxidative Burst of Neutrophils through Epac-Mediated Inhibition of Phospholipase C Activity, J. Immunol. Baltim. Md, vol.198, pp.1285-1296, 1950.

P. Glaser, H. Sakamoto, J. Bellalou, A. Ullmann, and A. Danchin, Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis, EMBO J, vol.7, pp.3997-4004, 1988.

J. Bellalou, H. Sakamoto, D. Ladant, C. Geoffroy, and A. Ullmann, Deletions affecting hemolytic and toxin activities of Bordetella pertussis adenylate cyclase, Infect. Immun, vol.58, pp.3242-3247, 1990.

I. E. Ehrmann, M. C. Gray, V. M. Gordon, L. S. Gray, and E. L. Hewlett, Hemolytic activity of adenylate cyclase toxin from Bordetella pertussis, FEBS Lett, vol.278, pp.79-83, 1991.

R. Benz, E. Maier, D. Ladant, A. Ullmann, and P. Sebo, Adenylate cyclase toxin (CyaA) of Bordetella pertussis. Evidence for the formation of small ion-permeable channels and comparison with HlyA of Escherichia coli, J. Biol. Chem, vol.269, pp.27231-27239, 1994.

G. Szabo, M. C. Gray, and E. L. Hewlett, Adenylate cyclase toxin from Bordetella pertussis produces ion conductance across artificial lipid bilayers in a calcium-and polarity-dependent manner, J. Biol. Chem, vol.269, pp.22496-22499, 1994.

M. Gray, G. Szabo, A. S. Otero, L. Gray, and E. Hewlett, Distinct mechanisms for K+ efflux, intoxication, and hemolysis by Bordetella pertussis AC toxin, J. Biol. Chem, vol.273, pp.18260-18267, 1998.

R. Fiser, J. Masin, M. Basler, J. Krusek, V. Spulakova et al., Third activity of Bordetella adenylate cyclase (AC) toxin-hemolysin. Membrane translocation of AC domain polypeptide promotes calcium influx into CD11b+ monocytes independently of the catalytic and hemolytic activities, J. Biol. Chem, vol.282, pp.2808-2820, 2007.

E. L. Hewlett, G. M. Donato, and M. C. Gray, Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: More than just making cyclic, AMP! Mol. Microbiol, vol.59, pp.447-459, 2006.

M. Basler, J. Masin, R. Osicka, and P. Sebo, Pore-forming and enzymatic activities of Bordetella pertussis adenylate cyclase toxin synergize in promoting lysis of monocytes, Infect. Immun, vol.74, pp.2207-2214, 2006.

K. C. Bagley, S. F. Abdelwahab, R. G. Tuskan, T. R. Fouts, and G. K. Lewis, Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway, J. Leukoc. Biol, vol.72, pp.962-969, 2002.

I. Adkins, J. Kamanova, A. Kocourkova, M. Svedova, J. Tomala et al., Bordetella adenylate cyclase toxin differentially modulates toll-like receptor-stimulated activation, migration and T cell stimulatory capacity of dendritic cells, PLoS ONE, vol.9, 2014.

S. R. Paccani, F. Dal-molin, M. Benagiano, D. Ladant, M. M. D'elios et al., Suppression of T-lymphocyte activation and chemotaxis by the adenylate cyclase toxin of Bordetella pertussis, Infect. Immun, vol.76, pp.2822-2832, 2008.

S. Rossi-paccani, M. Benagiano, N. Capitani, I. Zornetta, D. Ladant et al., The adenylate cyclase toxins of Bacillus anthracis and Bordetella pertussis promote Th2 cell development by shaping T cell antigen receptor signaling, PLoS Pathog, vol.5, 2009.

S. R. Paccani, F. Finetti, M. Davi, L. Patrussi, M. M. D'elios et al., The Bordetella pertussis adenylate cyclase toxin binds to T cells via LFA-1 and induces its disengagement from the immune synapse, J. Exp. Med, vol.208, 2011.

P. Glaser, D. Ladant, O. Sezer, F. Pichot, A. Ullmann et al., The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: Cloning and expression in Escherichia coli, Mol. Microbiol, vol.2, pp.277-284, 1988.

A. Rogel, J. E. Schultz, R. M. Brownlie, J. G. Coote, R. Parton et al., Bordetella pertussis adenylate cyclase: Purification and characterization of the toxic form of the enzyme, EMBO J, vol.8, pp.2755-2760, 1989.

E. M. Barry, A. A. Weiss, I. E. Ehrmann, M. C. Gray, E. L. Hewlett et al., Bordetella pertussis adenylate cyclase toxin and hemolytic activities require a second gene, cyaC, for activation, J. Bacteriol, vol.173, pp.720-726, 1991.

M. Hackett, L. Guo, J. Shabanowitz, D. F. Hunt, and E. L. Hewlett, Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis, Science, vol.266, pp.433-435, 1994.

G. D. Westrop, E. K. Hormozi, N. A. Da-costa, R. Parton, and J. G. Coote, Bordetella pertussis adenylate cyclase toxin: proCyaA and CyaC proteins synthesised separately in Escherichia coli produce active toxin in vitro, Gene, vol.180, pp.91-99, 1996.

P. Sebo, P. Glaser, H. Sakamoto, and A. Ullmann, High-level synthesis of active adenylate cyclase toxin of Bordetella pertussis in a reconstructed Escherichia coli system, Gene, vol.104, pp.19-24, 1991.

B. M. Laoide and A. Ullmann, Virulence dependent and independent regulation of the Bordetella pertussis cya operon, EMBO J, vol.9, pp.999-1005, 1990.

I. Linhartova, L. Bumba, J. Masin, M. Basler, R. Osicka et al., RTX proteins: A highly diverse family secreted by a common mechanism, FEMS Microbiol. Rev, vol.34, pp.1076-1112, 2010.

A. Chenal, A. C. Sotomayor-perez, and D. Ladant, Structure & function of RTX toxins, The Comprehensive Sourcebook of Bacterial Protein Toxins

J. Alouf, D. Ladant, M. R. Popoff, and . Eds, , pp.677-718, 2015.

D. Ladant, C. Brezin, J. M. Alonso, I. Crenon, and N. Guiso, Bordetella pertussis adenylate cyclase. Purification, characterization, and radioimmunoassay, J. Biol. Chem, vol.261, pp.16264-16269, 1986.
URL : https://hal.archives-ouvertes.fr/hal-02539736

H. Sakamoto, J. Bellalou, P. Sebo, and D. Ladant, Bordetella pertussis adenylate cyclase toxin. Structural and functional independence of the catalytic and hemolytic activities, J. Biol. Chem, vol.267, pp.13598-13602, 1992.

I. E. Ehrmann, A. A. Weiss, M. S. Goodwin, M. C. Gray, E. Barry et al., Enzymatic activity of adenylate cyclase toxin from Bordetella pertussis is not required for hemolysis, FEBS Lett, vol.304, pp.51-56, 1992.

J. Wolff, G. H. Cook, A. R. Goldhammer, and S. A. Berkowitz, Calmodulin activates prokaryotic adenylate cyclase, Proc. Natl. Acad. Sci, vol.77, pp.3841-3844, 1980.

D. Ladant, Interaction of Bordetella pertussis adenylate cyclase with calmodulin. Identification of two separated calmodulin-binding domains, J. Biol. Chem, vol.263, pp.2612-2618, 1988.

P. Glaser, A. Elmaoglou-lazaridou, E. Krin, D. Ladant, O. Barzu et al., Identification of residues essential for catalysis and binding of calmodulin in Bordetella pertussis adenylate cyclase by site-directed mutagenesis, EMBO J, vol.8, pp.967-972, 1989.

Q. Guo, Y. Shen, Y. Lee, C. S. Gibbs, M. Mrksich et al., Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin, EMBO J, vol.24, pp.3190-3201, 2005.

E. Selwa, M. Davi, A. Chenal, A. Sotomayor-perez, D. Ladant et al., Allosteric activation of Bordetella pertussis adenylyl cyclase by calmodulin: Molecular dynamics and mutagenesis studies, J. Biol. Chem, vol.289, pp.21131-21141, 2014.
URL : https://hal.archives-ouvertes.fr/pasteur-01107494

T. I. Springer, C. C. Emerson, C. W. Johns, and N. L. Finley, Interaction with adenylate cyclase toxin from Bordetella pertussis affects the metal binding properties of calmodulin, FEBS Open Bio, vol.7, pp.25-34, 2017.

D. P. O'brien, D. Durand, A. Voegele, V. Hourdel, M. Davi et al., Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis, PLoS Biol, vol.15, 2017.

M. Basler, O. Knapp, J. Masin, R. Fiser, E. Maier et al., Segments crucial for membrane translocation and pore-forming activity of Bordetella adenylate cyclase toxin, J. Biol. Chem, vol.282, pp.12419-12429, 2007.

R. A. Pandit, K. Meetum, K. Suvarnapunya, G. Katzenmeier, W. Chaicumpa et al., Isolated CyaA-RTX subdomain from Bordetella pertussis: Structural and functional implications for its interaction with target erythrocyte membranes, Biochem. Biophys. Res. Commun, vol.466, pp.76-81, 2015.

J. C. Karst, R. Barker, U. Devi, M. J. Swann, M. Davi et al., Identification of a region that assists membrane insertion and translocation of the catalytic domain of Bordetella pertussis CyaA toxin, J. Biol. Chem, vol.287, pp.9200-9212, 2012.
URL : https://hal.archives-ouvertes.fr/pasteur-01423063

O. Subrini, A. Sotomayor-perez, A. Hessel, J. Spiaczka-karst, E. Selwa et al., Characterization of a membrane-active peptide from the Bordetella pertussis CyaA toxin, J. Biol. Chem, vol.288, pp.32585-32598, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00937043

A. Voegele, O. Subrini, N. Sapay, D. Ladant, and A. Chenal, Membrane-Active Properties of an Amphitropic Peptide from the CyaA Toxin Translocation Region, Toxins, vol.9, p.369, 2017.

J. Masin, A. Osickova, A. Sukova, R. Fiser, P. Halada et al., Negatively charged residues of the segment linking the enzyme and cytolysin moieties restrict the membrane-permeabilizing capacity of adenylate cyclase toxin, Sci. Rep, 2016.

J. Vojtova-vodolanova, M. Basler, R. Osicka, O. Knapp, E. Maier et al., Oligomerization is involved in pore formation by Bordetella adenylate cyclase toxin, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol, vol.23, pp.2831-2843, 2009.

B. Powthongchin and C. Angsuthanasombat, Effects on haemolytic activity of single proline substitutions in the Bordetella pertussis CyaA pore-forming fragment, Arch. Microbiol, 0191.

C. Kurehong, C. Kanchanawarin, B. Powthongchin, P. Prangkio, G. Katzenmeier et al., Functional Contributions of Positive Charges in the Pore-Lining Helix 3 of the Bordetella pertussis CyaA-Hemolysin to Hemolytic Activity and Ion-Channel Opening, Toxins, vol.9, 2017.

T. Basar, V. Havlicek, S. Bezouskova, P. Halada, M. Hackett et al., The conserved lysine 860 in the additional fatty-acylation site of Bordetella pertussis adenylate cyclase is crucial for toxin function independently of its acylation status, J. Biol. Chem, vol.274, pp.10777-10783, 1999.

T. Basar, V. Havlicek, S. Bezouskova, M. Hackett, and P. Sebo, Acylation of lysine 983 is sufficient for toxin activity of Bordetella pertussis adenylate cyclase. Substitutions of alanine 140 modulate acylation site selectivity of the toxin acyltransferase CyaC, J. Biol. Chem, vol.276, pp.348-354, 2001.

J. C. Karst, V. Y. Ntsogo-enguene, S. E. Cannella, O. Subrini, A. Hessel et al., Calcium, acylation, and molecular confinement favor folding of Bordetella pertussis adenylate cyclase CyaA toxin into a monomeric and cytotoxic form, J. Biol. Chem, vol.289, pp.30702-30716, 2014.
URL : https://hal.archives-ouvertes.fr/pasteur-01408931

S. E. Cannella, V. Y. Ntsogo-enguene, M. Davi, C. Malosse, A. C. Sotomayor-perez et al., Stability, structural and functional properties of a monomeric, calcium-loaded adenylate cyclase toxin, CyaA, from Bordetella pertussis
URL : https://hal.archives-ouvertes.fr/pasteur-01508525

R. Benz, Channel formation by RTX-toxins of pathogenic bacteria: Basis of their biological activity, Biochim. Biophys. Acta, vol.1858, pp.526-537, 2016.

U. Baumann, S. Wu, K. M. Flaherty, and D. B. Mckay, Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: A two-domain protein with a calcium binding parallel beta roll motif, EMBO J, vol.12, pp.3357-3364, 1993.

L. Bumba, J. Masin, P. Macek, T. Wald, L. Motlova et al., Calcium-Driven Folding of RTX Domain beta-Rolls Ratchets Translocation of RTX Proteins through Type I Secretion Ducts, Mol. Cell, vol.62, pp.47-62, 2016.

E. Hanski and Z. Farfel, Bordetella pertussis invasive adenylate cyclase. Partial resolution and properties of its cellular penetration, J. Biol. Chem, vol.260, pp.5526-5532, 1985.

A. Rogel and E. Hanski, Distinct steps in the penetration of adenylate cyclase toxin of Bordetella pertussis into sheep erythrocytes. Translocation of the toxin across the membrane, J. Biol. Chem, vol.267, pp.22599-22605, 1992.

E. L. Hewlett, L. Gray, M. Allietta, I. Ehrmann, V. M. Gordon et al., Adenylate cyclase toxin from Bordetella pertussis. Conformational change associated with toxin activity, J. Biol. Chem, vol.266, pp.17503-17508, 1991.

T. Rose, P. Sebo, J. Bellalou, and D. Ladant, Interaction of calcium with Bordetella pertussis adenylate cyclase toxin. Characterization of multiple calcium-binding sites and calcium-induced conformational changes, J. Biol. Chem, vol.270, pp.26370-26376, 1995.

C. Bauche, A. Chenal, O. Knapp, C. Bodenreider, R. Benz et al., Structural and functional characterization of an essential RTX subdomain of Bordetella pertussis adenylate cyclase toxin, J. Biol. Chem, vol.281, pp.16914-16926, 2006.

A. Chenal, J. I. Guijarro, B. Raynal, M. Delepierre, and D. Ladant, RTX calcium binding motifs are intrinsically disordered in the absence of calcium: Implication for protein secretion, J. Biol. Chem, vol.284, pp.1781-1789, 2009.
URL : https://hal.archives-ouvertes.fr/pasteur-00364637

A. Chenal, J. C. Karst, A. C. Sotomayor-perez, A. K. Wozniak, B. Baron et al., Calcium-induced folding and stabilization of the intrinsically disordered RTX domain of the CyaA toxin, Biophys. J, vol.99, pp.3744-3753, 2010.
URL : https://hal.archives-ouvertes.fr/pasteur-01509576

A. Sotomayor-perez, O. Subrini, A. Hessel, D. Ladant, and A. Chenal, Molecular crowding stabilizes both the intrinsically disordered calcium-free state and the folded calcium-bound state of a repeat in toxin (RTX) protein, J. Am. Chem. Soc, vol.135, pp.11929-11934, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-01423043

D. P. O'brien, B. Hernandez, D. Durand, V. Hourdel, A. Sotomayor-perez et al., Structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion, Sci. Rep, vol.5, 2015.

D. P. O'brien, S. Brier, D. Ladant, D. Durand, A. Chenal et al., A powerful combination. The case of the calcium-binding domain of a bacterial toxin, Biotechnol. Appl. Biochem, vol.65, pp.62-68, 2018.

M. C. Gray, G. M. Donato, F. R. Jones, T. Kim, and E. L. Hewlett, Newly secreted adenylate cyclase toxin is responsible for intoxication of target cells by Bordetella pertussis, Mol. Microbiol, vol.53, pp.1709-1719, 2004.

P. Sebo and D. Ladant, Repeat sequences in the Bordetella pertussis adenylate cyclase toxin can be recognized as alternative carboxy-proximal secretion signals by the Escherichia coli alpha-haemolysin translocator, Mol. Microbiol, vol.9, pp.999-1009, 1993.

A. Rogel, R. Meller, and E. Hanski, Adenylate cyclase toxin from Bordetella pertussis. The relationship between induction of cAMP and hemolysis, J. Biol. Chem, vol.266, pp.3154-3161, 1991.

F. Dal-molin, F. Tonello, D. Ladant, I. Zornetta, I. Zamparo et al., Cell entry and cAMP imaging of anthrax edema toxin, EMBO J, vol.25, pp.5405-5413, 2006.

V. M. Gordon, W. W. Young, S. M. Lechler, M. C. Gray, S. H. Leppla et al., Adenylate cyclase toxins from Bacillus anthracis and Bordetella pertussis. Different processes for interaction with and entry into target cells, J. Biol. Chem, vol.264, pp.14792-14796, 1989.

J. Masin, M. Basler, O. Knapp, M. El-azami-el-idrissi, E. Maier et al., Acylation of lysine 860 allows tight binding and cytotoxicity of Bordetella adenylate cyclase on CD11b-expressing cells, Biochemistry (Mosc, vol.44, pp.12759-12766, 2005.

M. C. Gray, W. Ross, K. Kim, and E. L. Hewlett, Characterization of binding of adenylate cyclase toxin to target cells by flow cytometry, Infect. Immun, vol.67, pp.4393-4399, 1999.

J. Masin, I. Konopasek, J. Svobodova, and P. Sebo, Different structural requirements for adenylate cyclase toxin interactions with erythrocyte and liposome membranes, Biochim. Biophys. Acta, vol.1660, pp.144-154, 2004.

M. Bejerano, I. Nisan, A. Ludwig, W. Goebel, and E. Hanski, Characterization of the C-terminal domain essential for toxic activity of adenylate cyclase toxin, Mol. Microbiol, vol.31, pp.381-392, 1999.

J. Novak, O. Cerny, A. Osickova, I. Linhartova, J. Masin et al., Structure-Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes, Toxins, vol.9, 2017.

R. Veneziano, C. Rossi, A. Chenal, J. Devoisselle, D. Ladant et al., Bordetella pertussis adenylate cyclase toxin translocation across a tethered lipid bilayer, Proc. Natl. Acad. Sci, vol.110, pp.20473-20478, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00922119

D. Gonzalez-bullon, K. B. Uribe, C. Martin, and H. Ostolaza, Phospholipase A activity of adenylate cyclase toxin mediates translocation of its adenylate cyclase domain, Proc. Natl. Acad. Sci, vol.114, pp.6784-6793, 2017.

L. Bumba, J. Masin, A. Osickova, R. Osicka, and P. Sebo, Bordetella pertussis Adenylate Cyclase Toxin Does Not Possess a Phospholipase A Activity; Serine 606 and Aspartate 1079 Residues Are Not Involved in Target Cell Delivery of the Adenylyl Cyclase Enzyme Domain, Toxins, vol.10, p.245, 2018.

L. Bumba, J. Masin, R. Fiser, and P. Sebo, Bordetella adenylate cyclase toxin mobilizes its beta2 integrin receptor into lipid rafts to accomplish translocation across target cell membrane in two steps, PLoS Pathog, 2010.

G. Karimova, C. Fayolle, S. Gmira, A. Ullmann, C. Leclerc et al., Charge-dependent translocation of Bordetella pertussis adenylate cyclase toxin into eukaryotic cells: Implication for the in vivo delivery of CD8(+) T cell epitopes into antigen-presenting cells, Proc. Natl. Acad. Sci, vol.95, pp.12532-12537, 1998.

N. Khelef, P. Gounon, and N. Guiso, Internalization of Bordetella pertussis adenylate cyclase-haemolysin into endocytic vesicles contributes to macrophage cytotoxicity, Cell. Microbiol, vol.3, pp.721-730, 2001.

C. Martin, K. B. Uribe, G. Gomez-bilbao, and H. Ostolaza, Adenylate cyclase toxin promotes internalisation of integrins and raft components and decreases macrophage adhesion capacity, PLoS ONE, vol.6, 2011.

R. Fiser, J. Masin, L. Bumba, E. Pospisilova, C. Fayolle et al., Calcium influx rescues adenylate cyclase-hemolysin from rapid cell membrane removal and enables phagocyte permeabilization by toxin pores, PLoS Pathog, vol.8, 2012.

N. Khelef, H. Sakamoto, and N. Guiso, Both adenylate cyclase and hemolytic activities are required by Bordetella pertussis to initiate infection, Microb. Pathog, vol.12, pp.227-235, 1992.

K. Skopova, B. Tomalova, I. Kanchev, P. Rossmann, M. Svedova et al., Cyclic AMP-Elevating Capacity of Adenylate Cyclase Toxin-Hemolysin Is Sufficient for Lung Infection but Not for Full Virulence of Bordetella pertussis, Infect. Immun, vol.85, 2017.

D. Ladant, P. Glaser, and A. Ullmann, Insertional mutagenesis of Bordetella pertussis adenylate cyclase, J. Biol. Chem, vol.267, pp.2244-2250, 1992.

P. Guermonprez, C. Fayolle, G. Karimova, A. Ullmann, C. Leclerc et al., Bordetella pertussis adenylate cyclase toxin: A vehicle to deliver CD8-positive T-cell epitopes into antigen presenting cells, Methods Enzymol, vol.326, pp.527-542, 2000.

P. G. Coulie, B. J. Van-den-eynde, P. Van-der-bruggen, and T. Boon, Tumour antigens recognized by T lymphocytes: At the core of cancer immunotherapy, Nat. Rev. Cancer, vol.14, pp.135-146, 2014.

O. J. Finn, The dawn of vaccines for cancer prevention, Nat. Rev. Immunol, vol.18, pp.183-194, 2018.

P. Sebo, C. Fayolle, O. Andria, D. Ladant, C. Leclerc et al., Cell-invasive activity of epitope-tagged adenylate cyclase of Bordetella pertussis allows in vitro presentation of a foreign epitope to CD8+ cytotoxic T cells, Infect. Immun, vol.63, pp.3851-3857, 1995.

C. Fayolle, P. Sebo, D. Ladant, A. Ullmann, and C. Leclerc, In vivo induction of CTL responses by recombinant adenylate cyclase of Bordetella pertussis carrying viral CD8+ T cell epitopes, J. Immunol. Baltim. Md, vol.156, pp.4697-4706, 19501996.

P. Guermonprez, D. Ladant, G. Karimova, A. Ullmann, and C. Leclerc, Direct delivery of the Bordetella pertussis adenylate cyclase toxin to the MHC class I antigen presentation pathway, J. Immunol. Baltim. Md, vol.162, pp.1910-1916, 19501999.

G. Dadaglio, S. Morel, C. Bauche, Z. Moukrim, F. A. Lemonnier et al., Recombinant adenylate cyclase toxin of Bordetella pertussis induces cytotoxic T lymphocyte responses against HLA*0201-restricted melanoma epitopes, Int. Immunol, vol.15, pp.1423-1430, 2003.

G. Dadaglio, Z. Moukrim, R. Lo-man, V. Sheshko, P. Sebo et al., Induction of a polarized Th1 response by insertion of multiple copies of a viral, Infect. Immun, vol.68, pp.3867-3872, 2000.

J. Loucka, G. Schlecht, J. Vodolanova, C. Leclerc, and P. Sebo, Delivery of a MalE CD4(+)-T-cell epitope into the major histocompatibility complex class II antigen presentation pathway by Bordetella pertussis adenylate cyclase, Infect. Immun, vol.70, pp.1002-1005, 2002.

G. Schlecht, J. Loucka, H. Najar, P. Sebo, and C. Leclerc, Antigen targeting to CD11b allows efficient presentation of CD4+ and CD8+ T cell epitopes and in vivo Th1-polarized T cell priming, J. Immunol. Baltim. Md, vol.173, pp.6089-6097, 1950.

H. M. Vordermeier, M. Simsova, K. A. Wilkinson, R. J. Wilkinson, R. G. Hewinson et al., Recognition of mycobacterial antigens delivered by genetically detoxified Bordetella pertussis adenylate cyclase by T cells from cattle with bovine tuberculosis, Infect. Immun, vol.72, pp.6255-6261, 2004.

K. A. Wilkinson, M. Simsova, E. Scholvinck, P. Sebo, C. Leclerc et al., Efficient Ex vivo stimulation of Mycobacterium tuberculosis-specific T cells by genetically detoxified Bordetella pertussis adenylate cyclase antigen toxoids, Infect. Immun, vol.73, pp.2991-2998, 2005.

C. Fayolle, C. Bauche, D. Ladant, and C. Leclerc, Bordetella pertussis adenylate cyclase delivers chemically coupled CD8+ T-cell epitopes to dendritic cells and elicits CTL in vivo, vol.23, pp.604-614, 2004.

M. F. Saron, C. Fayolle, P. Sebo, D. Ladant, A. Ullmann et al., Anti-viral protection conferred by recombinant adenylate cyclase toxins from Bordetella pertussis carrying a CD8+ T cell epitope from lymphocytic choriomeningitis virus, Proc. Natl. Acad. Sci, vol.94, pp.3314-3319, 1997.

C. Fayolle, D. Ladant, G. Karimova, A. Ullmann, and C. Leclerc, Therapy of murine tumors with recombinant Bordetella pertussis adenylate cyclase carrying a cytotoxic T cell epitope, J. Immunol. Baltim. Md, vol.162, pp.4157-4162, 19501999.

S. Tartz, H. Russmann, J. Kamanova, P. Sebo, A. Sturm et al., Complete protection against P. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing Salmonella type III secretion system and Bordetella adenylate cyclase toxoid, vol.26, pp.5935-5943, 2008.

S. Gmira, G. Karimova, and D. Ladant, Characterization of recombinant Bordetella pertussis adenylate cyclase toxins carrying passenger proteins, Res. Microbiol, vol.152, pp.889-900, 2001.

S. H. Van-der-burg and C. J. Melief, Therapeutic vaccination against human papilloma virus induced malignancies, Curr. Opin. Immunol, vol.23, pp.252-257, 2011.

W. Ma, C. J. Melief, and S. Van-der-burg, Control of immune escaped human papilloma virus is regained after therapeutic vaccination, Curr. Opin. Virol, vol.23, pp.16-22, 2017.

S. Mittal and L. Banks, Molecular mechanisms underlying human papillomavirus E6 and E7 oncoprotein-induced cell transformation, Mutat. Res. Rev. Mutat. Res, vol.772, pp.23-35, 2017.

X. Preville, D. Ladant, B. Timmerman, and C. Leclerc, Eradication of established tumors by vaccination with recombinant Bordetella pertussis adenylate cyclase carrying the human papillomavirus 16 E7 oncoprotein, Cancer Res, vol.65, pp.641-649, 2005.

L. Majlessi, M. Simsova, Z. Jarvis, P. Brodin, M. Rojas et al., An increase in antimycobacterial Th1-cell responses by prime-boost protocols of immunization does not enhance protection against tuberculosis, Infect. Immun, vol.74, pp.2128-2137, 2006.

S. Hervas-stubbs, L. Majlessi, M. Simsova, J. Morova, M. Rojas et al., High frequency of CD4+ T cells specific for the TB10.4 protein correlates with protection against Mycobacterium tuberculosis infection, Infect. Immun, vol.74, pp.3396-3407, 2006.

B. Ensoli, A. Cafaro, P. Monini, S. Marcotullio, and F. Ensoli, Challenges in HIV Vaccine Research for Treatment and Prevention, Front. Immunol, vol.5, p.417, 2014.

G. E. Gray, F. Laher, E. Lazarus, B. Ensoli, and L. Corey, Approaches to preventative and therapeutic HIV vaccines, Curr. Opin. Virol, vol.17, pp.104-109, 2016.

L. Mascarell, C. Fayolle, C. Bauche, D. Ladant, and C. Leclerc, Induction of neutralizing antibodies and Th1-polarized and CD4-independent CD8+, J. Virol, vol.79, pp.9872-9884, 2005.

C. Fayolle, M. Davi, H. Dong, D. Ritzel, A. Le-page et al., Induction of anti-Tat neutralizing antibodies by the CyaA vector targeting dendritic cells: Influence of the insertion site and of the delivery of multicopies of the dominant Tat B-cell epitope, Vaccine, vol.28, pp.6930-6941, 2010.

L. Mascarell, C. Bauche, C. Fayolle, O. M. Diop, M. Dupuy et al., Delivery of the HIV-1 Tat protein to dendritic cells by the CyaA vector induces specific Th1 responses and high affinity neutralizing antibodies in non human primates, vol.24, pp.3490-3499, 2006.
URL : https://hal.archives-ouvertes.fr/pasteur-00566829

M. Esquerre, M. Momot, A. Goubier, C. Gonindard, S. Leung-theung-long et al., GTL001 and bivalent CyaA-based therapeutic vaccine strategies against human papillomavirus and other tumor-associated antigens induce effector and memory, vol.35, pp.1509-1516, 2017.

P. Guermonprez, C. Fayolle, M. Rojas, M. Rescigno, D. Ladant et al., In vivo receptor-mediated delivery of a recombinant invasive bacterial toxoid to CD11c + CD8 alpha -CD11bhigh dendritic cells, Eur. J. Immunol, vol.32, pp.3071-3081, 2002.

G. Fedele, I. Schiavoni, I. Adkins, N. Klimova, and P. Sebo, Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity, Toxins, vol.9, p.293, 2017.

G. Dadaglio, C. Fayolle, X. Zhang, B. Ryffel, M. Oberkampf et al., Antigen targeting to CD11b+ dendritic cells in association with TLR4/TRIF signaling promotes strong CD8+ T cell responses, J. Immunol. Baltim. Md, vol.193, pp.1787-1798, 1950.
URL : https://hal.archives-ouvertes.fr/pasteur-01942445

M. Svedova, J. Masin, R. Fiser, O. Cerny, J. Tomala et al., Pore-formation by adenylate cyclase toxoid activates dendritic cells to prime CD8 and CD4 T cells, Immunol. Cell Biol, vol.94, pp.322-333, 2016.
URL : https://hal.archives-ouvertes.fr/pasteur-01942437

A. Dunne, P. J. Ross, E. Pospisilova, J. Masin, A. Meaney et al., Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis, J. Immunol. Baltim. Md, vol.185, pp.1711-1719, 1950.

P. J. Ross, E. C. Lavelle, K. H. Mills, and A. P. Boyd, Adenylate cyclase toxin from Bordetella pertussis synergizes with lipopolysaccharide to promote innate interleukin-10 production and enhances the induction of Th2 and regulatory T cells, Infect. Immun, vol.72, pp.1568-1579, 2004.

K. Hormozi, R. Parton, and J. Coote, Adjuvant and protective properties of native and recombinant Bordetella pertussis adenylate cyclase toxin preparations in mice, FEMS Immunol. Med. Microbiol, vol.23, pp.273-282, 1999.

J. Macdonald-fyall, D. Xing, M. Corbel, S. Baillie, R. Parton et al., Adjuvanticity of native and detoxified adenylate cyclase toxin of Bordetella pertussis towards co-administered antigens, Vaccine, vol.22, pp.4270-4281, 2004.

P. Berraondo, C. Nouze, X. Preville, D. Ladant, and C. Leclerc, Eradication of large tumors in mice by a tritherapy targeting the innate, adaptive, and regulatory components of the immune system, Cancer Res, vol.67, pp.8847-8855, 2007.

M. Esquerre, M. Bouillette-marussig, A. Goubier, M. Momot, C. Gonindard et al., GTL001, a bivalent therapeutic vaccine against human papillomavirus 16 and 18, induces antigen-specific CD8+ T cell responses leading to tumor regression, PLoS ONE, vol.12, 2017.

P. Van-damme, M. Bouillette-marussig, A. Hens, I. De-coster, C. Depuydt et al., A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.22, pp.3238-3248, 2016.

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