The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes

• DOI: 10.1371/journal.ppat.1002356
• Publication Date: 2011-11-03T21:03:52Z
• Authors: Stephen Vadia; Eusondia Arnett; Anne-Cécile Haghi...; Elisabeth M. Wils...; Rodney K. Tweten; Stephanie Seveau
• Keywords: Listeriolysin O; Internalization; Cytolysin; Pore-forming toxin; Anthrax toxin

Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known express two invasins-InlA InlB-that induce bacterial internalization into nonphagocytic The pore-forming toxin listeriolysin O (LLO) facilitates escape from vesicle cytoplasm, where bacteria divide undergo cell-to-cell spreading via actin-based motility. In present study we demonstrate that in addition InlA InlB, LLO required for efficient of L. human hepatocytes (HepG2). Surprisingly, an invasion factor sufficient noninvasive innocua or polystyrene beads cells a dose-dependent fashion at concentrations produced by monocytogenes. To elucidate mechanisms underlying LLO-induced entry, constructed novel derivatives locked different stages assembly on membranes. We found bead entry only occurs upon pore formation. Scanning electron fluorescence microscopy studies show LLO-coated stimulate formation membrane extensions ingest early endosomal compartment. This pathway dynamin-and F-actin-dependent, clathrin-independent. Interestingly, further linking bacteria/bead uptake, induces F-actin polymerization tyrosine kinase-and pore-dependent fashion. conclusion, first time pathogen perforates cell plasma as strategy activate endocytic machinery gain cell.