Group : Actin-activated nucleotidyl cyclases

Bacterial adenylate cyclase toxins are potent virulence factors that synthesize cAMP to modulate or disable the function of the host cell. Pseudomonas aeruginosa, an opportunistic human pathogen that causes severe acute infections in immunocompromised individuals and is a major cause of chronic infections in cystic fibrosis patients, encodes a nucleotidyl cyclase (NC) toxin, called ExoY (here also termed PaExoY). PaExoY is one of the effectors that is injected directly into eukaryotic host cells by the type 3 secretion system (T3SS) of P. aeruginosa. To prevent detrimental effects to the native host, ExoY is inactive inside the bacterial cell and acquires catalytic activity only after its delivery to the eukaryotic host cell through interaction with a eukaryotic cofactor. We recently identified actin as the cofactor of ExoY in our laboratory. Once activated, ExoY can synthesize a variety of different cNMPs among them cyclic GMP (cGMP).
The ExoY-like module (VnExoY) found in the MARTX toxin (Multifunctional-Autoprocessing Repeats-in-ToXin) of Vibrio nigripulchritudo shares modest sequence similarity with PaExoY but is, nevertheless, also activated by actin. Our results established the existence of a new subgroup within the class II adenylate cyclase family, namely Actin-Activated Nucleotidyl Cyclases (AANC). We have first results showing that the AANC virulence factors despite sharing a common activator may actually display a greater variability of biological effects in infected cells than initially anticipated. We therefore aim to understand the function and diversities of ExoY-like/Actin-activated nucleotidyl cyclases from different bacterial species.