title: Bacillus cereus Certhrax ADP-ribosylates vinculin to disrupt focal adhesion complexes and cell adhesion.
abstract: Bacillus cereus is often associated with mild to moderate gastroenteritis; however, some recent isolates cause inhalational anthrax-like diseases and death. These potential emerging human pathogens express multiple virulence factors. B. cereus strain G9241 expresses anthrax toxin, several polysaccharide capsules, and the novel ADP-ribosyltransferase, Certhrax. In this study, we show that Certhrax ADP-ribosylates Arg-433 of vinculin, a protein that coordinates actin cytoskeleton and extracellular matrix interactions. ADP-ribosylation of vinculin disrupted focal adhesion complexes and redistributed vinculin to the cytoplasm. Exogenous vinculin rescued these phenotypes. This provides a mechanism for strain G9241 to breach host barrier defenses and promote bacterial growth and spread. Certhrax is the first bacterial toxin to add a post-translational modification to vinculin to disrupt the actin cytoskeleton.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Simon
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226. Electronic address: jtb01@mcw.edu.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Barbieri
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000378:metabolism; D001409:Bacillus cereus / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019809:Streptavidin; D016596:Vinculin / Q000378:metabolism*
chemical_list: D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D011994:Recombinant Proteins; C030325:anthrax toxin; D016596:Vinculin; D000246:Adenosine Diphosphate Ribose; D019809:Streptavidin; D036002:ADP Ribose Transferases; C578090:certhrax toxin, Bacillus cereus
keywords: ADP-ribosylation; Actin; Bacillus; Bacterial Toxins; Microscopic Imaging