title: Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles.
abstract: Listeria monocytogenes is an intracellular bacterial pathogen that replicates rapidly in the cytosol of host cells during acute infection. Surprisingly, these bacteria were found to occupy vacuoles in liver granuloma macrophages during persistent infection of severe combined immunodeficient (SCID) mice. Here we show that L. monocytogenes can replicate in vacuoles within macrophages. In livers of SCID mice infected for 21 days, we observed bacteria in large LAMP1(+) compartments that we termed spacious Listeria-containing phagosomes (SLAPs). SLAPs were also observed in vitro, and were found to be non-acidic and non-degradative compartments that are generated in an autophagy-dependent manner. The replication rate of bacteria in SLAPs was found to be reduced compared to the rate of those in the cytosol. Listeriolysin O (LLO, encoded by hly), a pore-forming toxin essential for L. monocytogenes virulence, was necessary and sufficient for SLAP formation. A L. monocytogenes mutant with low LLO expression was impaired for phagosome escape but replicated slowly in SLAPs over a 72 h period. Therefore, our studies reveal a role for LLO in promoting L. monocytogenes replication in vacuoles and suggest a mechanism by which this pathogen can establish persistent infection in host macrophages.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Birmingham
authors.forename: Veronica
authors.initials: V
authors.lastname: Canadien
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Kaniuk
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Steinberg
authors.forename: Darren E
authors.initials: DE
authors.lastname: Higgins
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D000818:Animals; D001343:Autophagy; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000382:microbiology; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000382:microbiology*; D051379:Mice; D016513:Mice, SCID; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology*; D014774:Virulence; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D051907:Lysosomal Membrane Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C038705:hlyA protein, Listeria monocytogenes