How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane

• DOI: 10.1242/jcs.114.24.4637
• Publication Date: 2021-04-26T00:34:58Z
• Authors: Lewis G. Tilney; Omar S. Harb; Patricia S. Connelly; Camenzind G. Robi...; Craig R. Roy
• Keywords: Organelles; 0303 health sciences; Time Factors; Cell Membrane; Membrane Proteins; Intracellular Membranes; U937 Cells; Cell Fractionation; Gram-Positive Bacteria; Lipid Metabolism; Legionella pneumophila; Mitochondria; Microscopy, Electron; 03 medical and health sciences; Bacterial Proteins; Phagosomes; Mutation; Humans; Carrier Proteins; Lysosomes; Ribosomes; Molecular Chaperones

Within five minutes of macrophage infection by Legionella pneumophila, the bacterium responsible for Legionnaires’ disease, elements of the rough endoplasmic reticulum (RER) and mitochondria attach to the surface of the bacteria-enclosed phagosome. Connecting these abutting membranes are tiny hairs, which are frequently periodic like the rungs of a ladder. These connections are stable and of high affinity - phagosomes from infected macrophages remain connected to the ER and mitochondria (as they were in situ) even after infected macrophages are homogenized. Thin sections through the plasma and phagosomal membranes show that the phagosomal membrane is thicker (72±2 Å) than the ER and mitochondrial membranes (60±2 Å), presumably owing to the lack of cholesterol, sphingolipids and glycolipids in the ER. Interestingly, within 15 minutes of infection, the phagosomal membrane changes thickness to resemble that of the attached ER vesicles. Only later (e.g. after six hours) does the ER-phagosome association become less frequent. Instead ribosomes stud the former phagosomal membrane and L. pneumophila reside directly in the rough ER. Examination of phagosomes of various L. pneumophila mutants suggests that this membrane conversion is a four-stage process used by L. pneumophila to establish itself in the RER and to survive intracellularly. But what is particularly interesting is that L. pneumophila is exploiting a poorly characterized naturally occuring cellular process.