+1 504 6082390
Scientific Tracks Abstracts: J Clinic Toxicol
B acterial pore-forming toxins (PFTs) constitute a major class of virulence factors that subvert host cells during pathogenesis. PFTs are synthesized as water soluble monomers that target the host cell plasma membrane and undergo conformational remodeling to form oligomeric transmembrane pores. These toxins exert a wide range of activities, from rapid killing of the target cell to subtle subversion of cellular functions. Cell lysis leads to the release of nutrients, advantaging proliferation of the bacterial pathogen. Cell lysis also weakens the host defense when PFTs target immune cells. At sub-lytic concentrations, PFTs only transiently compromise cellular permeability as plasma membrane repair machineries rapidly restore cell integrity. Nevertheless, ion and small molecule fluxes across the transiently perforated plasma membrane constitute �danger signals� that activate signaling networks and strongly affect cellular functions. Little is known about the sublytic activities of PFTs. Listeriolysin O belongs to the largest family bacterial PFTs, the cholesterol-dependent cytolysins, and is a most critical virulence factor of the facultative intracellular bacterial pathogen Listeria monocytogenes . We demonstrated that listeriolysin O can act as a bacterial invasin that induces L. monocytogenes internalization into host cells. We found that formation of listeriolysin O pore complexes is strictly required to activate F-actin- and dynamin-dependent internalization of the bacterium. Our findings indicate that host membrane perforation by a PFT can be used as an invasion strategy by L. monocytogenes and raise the hypothesis that other bacteria may use a similar entry pathway into host cells.
Stephanie Seveau has completed her PhD at the Pierre and Marie Curie University Paris, France and postdoctoral studies at the Weill Cornell Medical College New York, USA and Pasteur Institute Paris, France. She is an Assistant Professor in the Departments of Microbiology and Microbial Infection & Immunity at The Ohio State University, USA