{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:58:54Z","timestamp":1791298734397,"version":"4.1.0"},"reference-count":53,"publisher":"The Company of Biologists","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,12,15]]},"abstract":"<jats:p>Within five minutes of macrophage infection by Legionella pneumophila, the bacterium responsible for Legionnaires\u2019 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\u00b12 A\u030a) than the ER and mitochondrial membranes (60\u00b12 A\u030a), 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.<\/jats:p>","DOI":"10.1242\/jcs.114.24.4637","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:34:58Z","timestamp":1619397298000},"page":"4637-4650","source":"Crossref","is-referenced-by-count":320,"title":["How the parasitic bacterium <i>Legionella pneumophila<\/i> modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane"],"prefix":"10.1242","volume":"114","author":[{"given":"Lewis G.","family":"Tilney","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar S.","family":"Harb","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia S.","family":"Connelly","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camenzind G.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, Section of Microbial Pathogenesis, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig R.","family":"Roy","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, Section of Microbial Pathogenesis, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042600092403400_ANDREWS-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Andrews, H. L., Vogel, J. P. and Isberg. R. R. (1998). Identification of linked Legionella pneumophila genes essential for intracellular growth and evasion of the endocytic pathway. Infect. Immun. 66, 950-958.","DOI":"10.1128\/IAI.66.3.950-958.1998"},{"key":"2021042600092403400_BERGER-ETAL-1994","doi-asserted-by":"crossref","unstructured":"Berger, K. H., Merriam, J. J. and Isberg, R. R. (1994). Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene. Mol. Microbiol. 14, 809-822.","DOI":"10.1111\/j.1365-2958.1994.tb01317.x"},{"key":"2021042600092403400_BRETSCHER-AND-MUNRO-1993","doi-asserted-by":"crossref","unstructured":"Bretscher, M. S. and Munro, S. (1993). Cholesterol and the Golgi apparatus. Science261, 1280-1281.","DOI":"10.1126\/science.8362242"},{"key":"2021042600092403400_BROWNELL-ETAL-2001","doi-asserted-by":"crossref","unstructured":"Brownell, W. E., Spector, A. A., Raphael, R. M. and Popel, A. S. (2001). Micro- and nanomechanics of the cochlear outer hair cell. Annu. Rev. Biomed. Eng.3, 169-194.","DOI":"10.1146\/annurev.bioeng.3.1.169"},{"key":"2021042600092403400_BYRNE-AND-SWANSON-1998","doi-asserted-by":"crossref","unstructured":"Byrne, B. and Swanson, M. S. (1998). Expression of Legionella pneumophila virulence traits in response to growth conditions. Infect. Immun. 66, 3029-3034.","DOI":"10.1128\/IAI.66.7.3029-3034.1998"},{"key":"2021042600092403400_CAJAL-ETAL-1996A","doi-asserted-by":"crossref","unstructured":"Cajal, Y., Ghanta, J., Easwaran, K., Surolia, A. and Jain, M. K. (1996a). Specificity for the exchange of phospholipids through polymyxin B mediated intermembrane molecular contacts. Biochemistry35, 5684-5695.","DOI":"10.1021\/bi952703c"},{"key":"2021042600092403400_CAJAL-ETAL-1996B","doi-asserted-by":"crossref","unstructured":"Cajal, Y., Rogers, J., Berg, O. G. and Jain, M. K. (1996b). Intermembrane molecular contacts by polymyxin B mediate exchange of phospholipids. Biochemistry35, 299-308.","DOI":"10.1021\/bi9512408"},{"key":"2021042600092403400_CHRISTIE-AND-VOGEL-2000","doi-asserted-by":"crossref","unstructured":"Christie, P. J. and Vogel, J. P. (2000). Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells. Trends Microbiol. 8, 354-360.","DOI":"10.1016\/S0966-842X(00)01792-3"},{"key":"2021042600092403400_CLEMENS-AND-HORWITZ-1995","doi-asserted-by":"crossref","unstructured":"Clemens, D. L. and Horwitz, M. A. (1995). Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J. Exp. Med. 181, 257-270.","DOI":"10.1084\/jem.181.1.257"},{"key":"2021042600092403400_COERS-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Coers, J., Kagan, J. C., Matthews, M., Nagai, H., Zuckman, D. M. and Roy, C. R. (2000). Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Mol. Microbiol. 38, 719-736.","DOI":"10.1046\/j.1365-2958.2000.02176.x"},{"key":"2021042600092403400_CRAIG-AND-STAEHELIN-1988","unstructured":"Craig, S. and Staehelin, L. A. (1988). High pressure freezing of intact plant tissues. Evaluation and characterization of novel features of the endoplasmic reticulum and associated membrane systems. Eur. J. Cell Biol. 46, 81-93."},{"key":"2021042600092403400_DING-ETAL-1992","unstructured":"Ding, B., Turgeon, R. and Parthatsarathy, M. V. (1992). Substructure of freeze substituted plasmadesmata. Parasitology. 199, 28-41."},{"key":"2021042600092403400_DOBBELAERE-AND-HEUSSLER-1999","doi-asserted-by":"crossref","unstructured":"Dobbelaere, D. and Heussler, V. (1999). Transformation of leukocytes by Theileria parva and T. annulata. Annu. Rev. Microbiol. 53, 1-42.","DOI":"10.1146\/annurev.micro.53.1.1"},{"key":"2021042600092403400_FERRARI-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Ferrari, G., Langen, H., Naito, M. and Pieters, J. (1999). A coat protein on phagosomes involved in the intracellular survival of Mycobacteria. Cell97, 435-447.","DOI":"10.1016\/S0092-8674(00)80754-0"},{"key":"2021042600092403400_FINLAY-AND-FALKOW-1997","doi-asserted-by":"crossref","unstructured":"Finlay, B. B. and Falkow, S. (1997). Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61, 136-169.","DOI":"10.1128\/.61.2.136-169.1997"},{"key":"2021042600092403400_FORGE-1991","doi-asserted-by":"crossref","unstructured":"Forge, A. (1991). Structural features of the lateral walls in mammalian cochlear outer hair cells. Cell Tissue Res. 265, 473-483.","DOI":"10.1007\/BF00340870"},{"key":"2021042600092403400_GAO-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Gao, L. Y., Susa, M., Ticac, B. and Abu Kwaik, Y. (1999). Heterogeneity in intracellular replication and cytopathogenicity of Legionella pneumophila and Legionella micdadei in mammalian and protozoan cells. Microb. Pathog. 27, 273-287.","DOI":"10.1006\/mpat.1999.0308"},{"key":"2021042600092403400_GATFIELD-AND-PIETERS-2000","doi-asserted-by":"crossref","unstructured":"Gatfield, J. and Pieters, J. (2000). Essential role for cholesterol in entry of Mycobacteria into macrophages. Science288, 1647-1650.","DOI":"10.1126\/science.288.5471.1647"},{"key":"2021042600092403400_GERHARDT-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Gerhardt, H., Walz, M. J., Faigle, M., Northoff, H., Wolburg, H. and Neumeister, B. (2000). Localization of Legionella bacteria within ribosome-studded phagosomes is not restricted to Legionella pneumophila. FEMS Microbiol. Lett. 192, 145-152.","DOI":"10.1111\/j.1574-6968.2000.tb09373.x"},{"key":"2021042600092403400_GRABSKI-ETAL-1993","doi-asserted-by":"crossref","unstructured":"Grabski, S., de Feijter, A. W. and Schindler, M. (1993). Endoplasmic reticulum forms a dynamic continuum for lipid diffusion between contiguous soybean root cells. The Plant Cell. 5, 25-38.","DOI":"10.2307\/3869425"},{"key":"2021042600092403400_HALL-1993","doi-asserted-by":"crossref","unstructured":"Hall, B. F. (1993). Trypanosoma cruzi: mechanisms for entry into host cells. Semin. Cell Biol. 4, 323-333.","DOI":"10.1006\/scel.1993.1039"},{"key":"2021042600092403400_HARB-AND-ABU-KWAIK-1998","doi-asserted-by":"crossref","unstructured":"Harb, O. S. and Abu Kwaik, Y. (1998). Identification of the aspartate-beta-semialdehyde dehydrogenase gene of Legionella pneumophila and characterization of a null mutant. Infect. Immun. 66, 1898-1903.","DOI":"10.1128\/IAI.66.5.1898-1903.1998"},{"key":"2021042600092403400_HARB-AND-ABU-KWAIK-2000","doi-asserted-by":"crossref","unstructured":"Harb, O. S. and Abu Kwaik, Y. (2000). Essential role for the Legionella pneumophila rep helicase homologue in intracellular infection of mammalian cells. Infect. Immun. 68, 6970-6978.","DOI":"10.1128\/IAI.68.12.6970-6978.2000"},{"key":"2021042600092403400_HARB-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Harb, O. S., Gao, L. Y. and Abu Kwaik, Y. (2000). From protozoa to mammalian cells: a new paradigm in the life cycle of intracellular bacterial pathogens. Environ. Microbiol. 2, 251-265.","DOI":"10.1046\/j.1462-2920.2000.00112.x"},{"key":"2021042600092403400_HEINZEN-ETAL-1996","doi-asserted-by":"crossref","unstructured":"Heinzen, R. A., Scidmore, M. A., Rockey, D. D. and Hackstadt, T. (1996). Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis. Infect. Immun. 64, 796-809.","DOI":"10.1128\/IAI.64.3.796-809.1996"},{"key":"2021042600092403400_HENKART-ETAL-1976","doi-asserted-by":"crossref","unstructured":"Henkart, M., Landis, D. M. and Reese, T. S. (1976). Similarity of junctions between plasma membranes and endoplasmic reticulum in muscle and neurons. J. Cell Biol. 70, 338-347.","DOI":"10.1083\/jcb.70.2.338"},{"key":"2021042600092403400_HIGH-ETAL-1992","doi-asserted-by":"crossref","unstructured":"High, N., Mounier, J., Prevost, M. C. and Sansonetti, P. J. (1992). IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 11, 1991-1999.","DOI":"10.1002\/j.1460-2075.1992.tb05253.x"},{"key":"2021042600092403400_HORWITZ-1983","doi-asserted-by":"crossref","unstructured":"Horwitz, M. A. (1983). Formation of a novel phagosome by the Legionnaires\u2019 disease bacterium (Legionella pneumophila) in human monocytes. J. Exp. Med. 158, 1319-1331.","DOI":"10.1084\/jem.158.4.1319"},{"key":"2021042600092403400_KARTENBECK-ETAL-1989","doi-asserted-by":"crossref","unstructured":"Kartenbeck, J., Stukenbrok, H. and Helenius, A. (1989). Endocytosis of simian virus 40 into the endoplasmic reticulum. J. Cell Biol. 109, 2721-2729.","DOI":"10.1083\/jcb.109.6.2721"},{"key":"2021042600092403400_KIM-AND-KLIONSKY-2000","doi-asserted-by":"crossref","unstructured":"Kim, J. and Klionsky, D. J. (2000). Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells. Annu. Rev. Biochem. 69, 303-342.","DOI":"10.1146\/annurev.biochem.69.1.303"},{"key":"2021042600092403400_LANGE-AND-DRSQUOALESSANDRO-1977","doi-asserted-by":"crossref","unstructured":"Lange, Y. and D\u2019Alessandro, J. S. (1977). Characterization of mechanisms for transfer of cholesterol between human erythrocytes and plasma. Biochemistry16, 4339-4343.","DOI":"10.1021\/bi00639a002"},{"key":"2021042600092403400_MATTHEWS-AND-ROY-2000","doi-asserted-by":"crossref","unstructured":"Matthews, M. and Roy, C. R. (2000). Identification and subcellular localization of the Legionella pneumophila IcmX protein: a factor essential for establishment of a replicative organelle in eukaryotic host cells. Infect. Immun. 68, 3971-3982.","DOI":"10.1128\/IAI.68.7.3971-3982.2000"},{"key":"2021042600092403400_NEZIL-AND-BLOOM-1992","doi-asserted-by":"crossref","unstructured":"Nezil, F. A. and Bloom, M. (1992). Combined influence of cholesterol and synthetic amphiphillic peptides upon bilayer thickness in model membranes. Biophys. J. 61, 1176-1183.","DOI":"10.1016\/S0006-3495(92)81926-4"},{"key":"2021042600092403400_PELKMANS-ETAL-2001","doi-asserted-by":"crossref","unstructured":"Pelkmans, L., Kartenbeck, J. and Helenius, A. (2001). Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat. Cell Biol. 5, 473-483.","DOI":"10.1038\/35074539"},{"key":"2021042600092403400_PIZARRO-CERDA-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Pizarro-Cerda, J., Meresse, S., Parton, R. G., van der Goot, G., Sola-Landa, A., Lopez-Goni, I., Moreno, E. and Gorvel, J. P. (1998). Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes. Infect. Immun. 66, 5711-5724.","DOI":"10.1128\/IAI.66.12.5711-5724.1998"},{"key":"2021042600092403400_POLLICE-AND-BROWNELL-1993","doi-asserted-by":"crossref","unstructured":"Pollice, P. A. and Brownell, W. E. (1993). Characterization of the outer hair cell\u2019s lateral wall membranes. Hear. Res. 70, 187-196.","DOI":"10.1016\/0378-5955(93)90157-V"},{"key":"2021042600092403400_PORTNOY-AND-JONES-1994","doi-asserted-by":"crossref","unstructured":"Portnoy, D. A. and Jones, S. (1994). The cell biology of Listeria monocytogenes infection (escape from a vacuole). Ann. NY Acad. Sci. 730, 15-25.","DOI":"10.1111\/j.1749-6632.1994.tb44235.x"},{"key":"2021042600092403400_ROY-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Roy, C. R., Berger, K. H. and Isberg, R. R. (1998). Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake. Mol. Microbiol. 28, 663-674.","DOI":"10.1046\/j.1365-2958.1998.00841.x"},{"key":"2021042600092403400_SADOSKY-ETAL-1993","doi-asserted-by":"crossref","unstructured":"Sadosky, A. B., Wiater, L. A. and Shuman, H. A. (1993). Identification of Legionella pneumophila genes required for growth within and killing of human macrophages. Infect. Immun. 61, 5361-5373.","DOI":"10.1128\/IAI.61.12.5361-5373.1993"},{"key":"2021042600092403400_SANDSTROM-AND-NILSSON-1976","doi-asserted-by":"crossref","unstructured":"Sandstrom, C. and Nilsson, K. (1976). Establishment and characterization of a human histocytic lymphoma cell line (U937). Int. J. Cancer. 17, 565-577.","DOI":"10.1002\/ijc.2910170504"},{"key":"2021042600092403400_SEGAL-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Segal, G., Purcell, M. and Shuman, H. A. (1998). Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. Proc. Natl. Acad. Sci. USA. 95, 1669-1674.","DOI":"10.1073\/pnas.95.4.1669"},{"key":"2021042600092403400_SEGAL-AND-SHUMAN-1997","doi-asserted-by":"crossref","unstructured":"Segal, G. and Shuman, H. A. (1997). Characterization of a new region required for macrophage killing by Legionella pneumophila. Infect. Immun. 65, 5057-5066.","DOI":"10.1128\/IAI.65.12.5057-5066.1997"},{"key":"2021042600092403400_SIBLEY-1993","doi-asserted-by":"crossref","unstructured":"Sibley, L. D. (1993). Interactions between Toxoplasma gondii and its mammalian host cells. Semin. Cell Biol. 4, 335-344.","DOI":"10.1006\/scel.1993.1040"},{"key":"2021042600092403400_SIMONS-AND-IKONEN-1997","doi-asserted-by":"crossref","unstructured":"Simons, K. and Ikonen, E. (1997). Functional rafts in cell membranes. Nature387, 569-572.","DOI":"10.1038\/42408"},{"key":"2021042600092403400_SIMONS-AND-IKONEN-2000","doi-asserted-by":"crossref","unstructured":"Simons, K. and Ikonen, E. (2000). How cells handle cholesterol. Science290, 1721-1726.","DOI":"10.1126\/science.290.5497.1721"},{"key":"2021042600092403400_SINAI-ETAL-1997","doi-asserted-by":"crossref","unstructured":"Sinai, A. P., Webster, P. and Joiner, K. A. (1997). Association of host cell endoplasmic reticulum and mitochondria with the Toxoplasma gondii parasitophorous vacuole membrane: a high affinity interaction. J. Cell Sci. 110, 2117-2128.","DOI":"10.1242\/jcs.110.17.2117"},{"key":"2021042600092403400_SLOTTE-AND-BIERMAN-1987","doi-asserted-by":"crossref","unstructured":"Slotte, J. P. and Bierman, E. L. (1987). Movement of plasma-membrane sterols to the endoplasmic reticulum in cultured cells. Biochem. J. 248, 237-242.","DOI":"10.1042\/bj2480237"},{"key":"2021042600092403400_STAEHELIN-1997","doi-asserted-by":"crossref","unstructured":"Staehelin, L. A. (1997). The plant ER: a dynamic organelle composed of a large number of discrete functional domains. Plant J. 11, 1151-1165.","DOI":"10.1046\/j.1365-313X.1997.11061151.x"},{"key":"2021042600092403400_SWANSON-AND-HAMMER-2000","doi-asserted-by":"crossref","unstructured":"Swanson, M. S. and Hammer, B. K. (2000). Legionella pneumophila pathogenesis: a fateful journey from amoebae to macrophages. Annu. Rev. Microbiol. 54,567-613.","DOI":"10.1146\/annurev.micro.54.1.567"},{"key":"2021042600092403400_SWANSON-AND-ISBERG-1995","doi-asserted-by":"crossref","unstructured":"Swanson, M. S. and Isberg, R. R. (1995). Association of Legionella pneumophila with the macrophage endoplasmic reticulum. Infect. Immun. 63, 3609-3620.","DOI":"10.1128\/IAI.63.9.3609-3620.1995"},{"key":"2021042600092403400_TILNEY-ETAL-1991","doi-asserted-by":"crossref","unstructured":"Tilney, L. G., Cooke, T. J., Connelly, P. S. and Tilney, M. S. (1991). The structure of plasmodesmata as revealed by plasmolysis, detergent extraction, and protease digestion. J. Cell Biol. 112, 739-747.","DOI":"10.1083\/jcb.112.4.739"},{"key":"2021042600092403400_VOGEL-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Vogel, J. P., Andrews, H. L., Wong, S. K. and Isberg, R. R. (1998). Conjugative transfer by the virulence system of Legionella pneumophila. Science279, 873-876.","DOI":"10.1126\/science.279.5352.873"},{"key":"2021042600092403400_WIATER-ETAL-1998","doi-asserted-by":"crossref","unstructured":"Wiater, L. A., Dunn, K., Maxfield, F. R. and Shuman, H. A. (1998). Early events in phagosome establishment are required for intracellular survival of Legionella pneumophila. Infect. Immun. 66, 4450-4460.","DOI":"10.1128\/IAI.66.9.4450-4460.1998"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/114\/24\/4637\/1359207\/4637.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/114\/24\/4637\/1359207\/4637.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:35:20Z","timestamp":1619397320000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/114\/24\/4637\/35726\/How-the-parasitic-bacterium-Legionella-pneumophila"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,12,15]]},"references-count":53,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2001,12,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.114.24.4637","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2001,12,15]]}}}