Avoiding death by autophagy: interactions of Listeria monocytogenes with the macrophage autophagy system.
Autophagy restricts the growth of a variety of intracellular pathogens. However, cytosol-adapted pathogens have evolved ways to evade restriction by this innate immune mechanism. Listeria monocytogenes is a Gram-positive bacterial pathogen that utilizes a cholesterol-dependent pore-forming toxin, listeriolysin O (LLO), to escape from the phagosome. Autophagy targets L. monocytogenes in LLO-damaged phagosomes and also in the cytosol under some experimental conditions. However, this bacterium has evolved multiple mechanisms to evade restriction by autophagy, including actin-based motility in the cytosol and an as yet undefined mechanism mediated by bacterial phospholipases C (PLCs). A population of L. monocytogenes with inefficient LLO activity forms Spacious Listeria-containing Phagosomes (SLAPs), which are autophagosome-like compartments that do not mature, allowing slow bacterial growth within enlarged vesicles. SLAPs may represent a stalemate between bacterial LLO action and the host autophagy system, resulting in persistent infection.
Birmingham
Cheryl L
CL
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Higgins
Darren E
DE
Brumell
John H
JH
D000199:Actins / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology; D001427:Bacterial Toxins; D003600:Cytosol / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology; D006460:Hemolysin Proteins / Q000502:physiology; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D010588:Phagosomes / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D010738:Type C Phospholipases; C038705:hlyA protein, Listeria monocytogenes