title: Listeriolysin O suppresses phospholipase C-mediated activation of the microbicidal NADPH oxidase to promote Listeria monocytogenes infection.
abstract: The intracellular bacterial pathogen Listeria monocytogenes produces phospholipases C (PI-PLC and PC-PLC) and the pore-forming cytolysin listeriolysin O (LLO) to escape the phagosome and replicate within the host cytosol. We found that PLCs can also activate the phagocyte NADPH oxidase during L. monocytogenes infection, a response that would adversely affect pathogen survival. However, secretion of LLO inhibits the NADPH oxidase by preventing its localization to phagosomes. LLO-deficient bacteria can be complemented by perfringolysin O, a related cytolysin, suggesting that other pathogens may also use pore-forming cytolysins to inhibit the NADPH oxidase. Our studies demonstrate that while the PLCs induce antimicrobial NADPH oxidase activity, this effect is alleviated by the pore-forming activity of LLO. Therefore, the combined activities of PLCs and LLO on membrane lysis and the inhibitory effects of LLO on NADPH oxidase activity allow L. monocytogenes to efficiently escape the phagosome while avoiding the microbicidal respiratory burst.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Lam
authors.forename: Ramzi
authors.initials: R
authors.lastname: Fattouh
authors.forename: Aleixo M
authors.initials: AM
authors.lastname: Muise
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
authors.forename: Darren E
authors.initials: DE
authors.lastname: Higgins
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D004789:Enzyme Activation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008089:Listeria monocytogenes / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D008088:Listeriosis / Q000201:enzymology* / Q000235:genetics / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D019255:NADPH Oxidases; D010738:Type C Phospholipases; C038705:hlyA protein, Listeria monocytogenes