TY - JOUR T1 - Actin activates <em>Pseudomonas aeruginosa</em> ExoY nucleotidyl cyclase toxin and ExoY-like effector domains from MARTX toxins JF - bioRxiv DO - 10.1101/032201 SP - 032201 AU - Dorothée Raoux-Barbot AU - Cosmin Saveanu AU - Abdelkader Namane AU - Vasily Ogryzko AU - Lina Worpenberg AU - Souad Fellous AU - Elodie Assayag AU - Daniel Ladant AU - Louis Renault AU - Undine Mechold Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/11/18/032201.abstract N2 - Pseudomonas aeruginosa is a major cause of chronic infections in cystic fibrosis patients. The nucleotidyl cyclase toxin ExoY is a virulence factors injected by the pathogen and associated with severe damage to lung tissue. ExoY-like cyclases are also found in other Gram-negative pathogens and shown to contribute to virulence, although they remained poorly characterized. Here we demonstrate that filamentous actin (F-actin) is the hitherto unknown co-factor that activates P. aeruginosa ExoY within host target cells. Highly purified actin, when polymerized into filaments, potently stimulates (&gt;10,000 fold) ExoY activity. ExoY co-localizes in vivo with actin filaments in transfected cells and, in vitro, it interferes with the regulation of actin assembly/disassembly-dynamics mediated by important F-actin-binding proteins. We further show that actin also activates an ExoY-like adenylate cyclase from a Vibrio species. Our results thus highlight a new sub-class within the class II adenylyl cyclase family, defined as actin-activated nucleotidyl cyclase (AA-NC) toxins. ER -