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Snapshots on Secretion, Folding, Translocation and Functions of the Bordetella pertussis CyaA Toxin

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Date and time 07.11.2016 12:15  
Place and room
Speaker Alexandre Chenal, Institut Pasteur, Paris (F)
Category Conferences - Seminars
joint BIOLOGICAL & STATISTICAL PHYSICS / BIOENGINEERING SEMINAR
(sandwiches served)

Abstract:
The adenylate cyclase toxin (CyaA, 1706 residues) plays an essential role in the early stages of respiratory tract colonization by Bordetella pertussis, the causative agent of whooping cough. The cell intoxication process, which is still poorly understood, involves a unique mechanism of translocation of the CyaA catalytic domain (AC) directly across the plasma membrane of target cells. Once in the cytosol, AC interacts with calmodulin (CaM) and produces supraphysiological levels of cAMP, leading to cell death. I will present some recent results covering several steps of the intoxication process, from toxin secretion to the AC:CaM complex formation.

Our data illustrate the structural flexibility of bacterial toxins adapted to various functions (such as secretion and enzymatic complex formation) and coupled to large variations in calcium concentrations encountered in the successive environments during the intoxication process. Moreover, we recently showed that the translocation process is dependent on (i) the electrochemical gradient across the membrane and (ii) the unique properties of a short CyaA region that mimics membrane-active peptides. Finally, due to its hydrophobic character, CyaA toxins do aggregate into multimeric forms in the absence of chaotropic agents in vitro.

We have recently defined the experimental conditions required for CyaA folding into a stable, monomeric and functional form. This opens new perspectives for both basic sciences and CyaA-based biotechnological applications developed in the lab, i.e., to improve antigen delivery vehicles and new pertussis vaccines.

Bio:
2010: HDR, Paris VII
2006: permanent position in BIM Unit, Institut Pasteur, Paris
2005-06: post-doc in Daniel Ladant Unit, Institut Pasteur, Paris
2004-05: post-doc in Daniel Gillet Unit, CEA
2002-03: post-doc in Florent Guillain group, CEA-CNRS, Grenoble
2001-1999 : PhD (DIEP, CEA Saclay) ED 227, MNHN, Paris
1998 : M2 D.E.A. n° 950 103, MNHN, P. VII, ESPCI, Paris
1997 : M1 Maîtrise de Biologie Moléculaire et Cellulaire option Physiologie, (UPMC, P. VI), Paris
1996 : Licence de Biologie Moléculaire et Cellulaire, UPMC (P. VI), Paris
1995 : D.E.U.G. de Biologie des Organismes, UPMC (P. VI), Paris

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