Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca2+-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair...

Pore-forming toxins (PFTs) represent the largest known group of bacterial protein toxins to date. Membrane insertion and subsequent pore-formation occurs after initial binding to cell-surface receptor and oligomerization. Aerolysin, a toxin produced by the Gram-negative bacterium Aeromonas hydrophila and related species, belongs to the PFT group and shares a common mechanism of action involving...

Aerolysin is a major virulence factor produced by the Gram-negative bacterium Aeromonas hydrophila and is a member of the β-pore-forming toxin family. Two oligomerization-deficient aerolysin mutants, H132D and H132N, have been overproduced, proteolyzed by trypsin digestion and purified. Crystals were grown from the proteolyzed forms and diffraction data were collected for the two mutants to 2.1...

Programmed necrosis is a mechanism of cell death that has been described for neuronal excitotoxicity and ischemia/reperfusion injury, but has not been extensively studied in the context of exposure to bacterial exotoxins. The alpha-toxin of Clostridium septicum is a beta-barrel pore-forming toxin and a potent cytotoxin; however, the mechanism by which it induces cell death has not been elucidat...

The plethora of virulence factors associated with Staphylococcus aureus make this bacterium an attractive candidate for a molecularly-designed epitope-focused vaccine. This approach, which necessitates the identification of neutralizing epitopes for incorporation into a vaccine construct, is being evaluated for pathogens where conventional approaches have failed to elicit protective humoral res...

After binding to cellular receptors and proteolytic activation, the protective antigen component of anthrax toxin forms a heptameric prepore. The prepore later undergoes pH-dependent conversion to a pore, mediating translocation of the edema and lethal factors to the cytosol. We describe structures of the prepore (3.6 A) and a prepore:receptor complex (4.3 A) that reveal the location of pore-fo...

Delta-toxin produced by Clostridium perfringens types B and C is a β-pore-forming cytotoxin. Here, using site-directed mutagenesis, we identified the amino acid residues that contribute to delta-toxin oligomerization binding. We replaced Lys-43 Ser-109 located in β-sandwich domain Arg-200 rim domain. Substitution of alanine for caused reductions both cytotoxicity oligomerization. However, excha...

Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently ...

BACKGROUND & OBJECTIVES Vibrio cholerae cytolysin/hemolysin (VCC) is a 65 kDa pore-forming toxin (PFT) secreted by O1 El Tor and non-O1 strains. The purified toxin, which contains two C-terminus carbohydrate-binding domains in addition to the cytolytic domain at the core, causes lysis of a wide spectrum of eukaryotic cells at picomolar concentrations, apoptogenesis of intestinal and immune cell...