Actin activates Pseudomonas aeruginosa ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins

Alexander Belyy, Dorothée Raoux-Barbot, Cosmin Saveanu, Abdelkader Namane, Vasily Ogryzko, Lina Worpenberg, Violaine David, Veronique Henriot, Souad Fellous, Christien Merrifield, Elodie Assayag, Daniel Ladant, Louis Renault () and Undine Mechold ()
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Alexander Belyy: Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires
Dorothée Raoux-Barbot: Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires
Cosmin Saveanu: Institut Pasteur, CNRS UMR3525, Génétique des Interactions Macromoléculaires
Abdelkader Namane: Institut Pasteur, CNRS UMR3525, Génétique des Interactions Macromoléculaires
Vasily Ogryzko: Institut Gustave Roussy, CNRS UMR 8126, Unité de Signaling, Nuclei and Innovations in Oncology
Lina Worpenberg: Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires
Violaine David: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Veronique Henriot: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Souad Fellous: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Christien Merrifield: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Elodie Assayag: Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires
Daniel Ladant: Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires
Louis Renault: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay
Undine Mechold: Institut Pasteur, CNRS UMR3528, Unité de Biochimie des Interactions Macromoléculaires

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract The nucleotidyl cyclase toxin ExoY is one of the virulence factors injected by the Pseudomonas aeruginosa type III secretion system into host cells. Inside cells, it is activated by an unknown eukaryotic cofactor to synthesize various cyclic nucleotide monophosphates. ExoY-like adenylate cyclases are also found in Multifunctional-Autoprocessing Repeats-in-ToXin (MARTX) toxins produced by various Gram-negative pathogens. Here we demonstrate that filamentous actin (F-actin) is the hitherto unknown cofactor of ExoY. Association with F-actin stimulates ExoY activity more than 10,000 fold in vitro and results in stabilization of actin filaments. ExoY is recruited to actin filaments in transfected cells and alters F-actin turnover. Actin also activates an ExoY-like adenylate cyclase MARTX effector domain from Vibrio nigripulchritudo. Finally, using a yeast genetic screen, we identify actin mutants that no longer activate ExoY. Our results thus reveal a new sub-group within the class II adenylyl cyclase family, namely actin-activated nucleotidyl cyclase (AA-NC) toxins.

Date: 2016
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DOI: 10.1038/ncomms13582

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