Biophysical characterisation of the translocation process of the CyaA toxin – TransloXyaA
The adenylate cyclase (CyaA) is an essential key virulence factor of Bordetella pertussis that displays the unique capability of delivering its catalytic domain directly across the plasma membrane of eukaryotic target cells. Yet, the molecular mechanisms involved in this remarkable process remain largely unknown. In this context, our project will contribute to the characterization of this original mechanism of cell invasion by biophysical approaches. In particular, we will study the physico-chemical properties of CyaA in solution in order to characterize the molecular events that precede the translocation process. Then, we will investigate the translocation process of the catalytic domain across model membrane systems and into eukaryotic cells. Thus, this project should lead to a better understanding of the successive steps involved in the cell intoxication mechanism and reveal the interactions between CyaA and membranes during this process. In addition, CyaA properties have been exploited to develop innovative vaccine vectors that will soon be tested in phase I/II of clinical trials. Data obtained on the physico-chemical properties of CyaA in solution and on the translocation process will be crucial for clinical developments of this molecule and its use in antitumoral immunotherapy.
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
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