{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:17:29Z","timestamp":1791267449201,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Legionella\npneumophila<\/jats:italic>\n            replicates within alveolar macrophages, causing a\nsevere pneumonia termed Legionnaires' disease. The bacterium resides\nwithin a vacuole that escapes immediate transport to the host lysosome.\nInstead, the vacuole interacts with the early secretory pathway to\nestablish an environment suitable for rapid multiplication. A type IV\nsecretion system is central to the pathogenicity of the bacterium, and\nmany protein substrates that are translocated by this system to the\nhost cell have been identified. One of these, VipD, was found to\ninterrupt the late secretory pathway when overproduced in\n            <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n            . We independently identified VipD in\na previous study and have further characterized this protein as well as\nits three paralogs. The\n            <jats:italic>vipD<\/jats:italic>\n            gene belongs to a family of\n            <jats:italic>L. pneumophila<\/jats:italic>\n            open reading frames that are predicted to\ncontain a phospholipase A domain with sequence similarity to the type\nIII-secreted toxin ExoU from\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            . Similarly\nto other known translocated proteins of\n            <jats:italic>L. pneumophila<\/jats:italic>\n            , VipD\nis strongly induced in early stationary phase, a time when the\nbacterium is most virulent. Detergent extraction studies of infected\nmacrophages confirm that VipD is translocated into host cells via the\ntype IV secretion system. A second assay for translocation revealed\nthat two paralogs of VipD, VpdA and VpdB, also have translocation\nsignals recognized by the type IV system. A strain lacking VipD and its\nthree paralogs grew at wild-type rates in murine macrophages, although\nsecondary mutations that cause growth defects in strains lacking VipD\naccumulate. The quadruple mutant displayed a growth advantage in the\namoebal host\n            <jats:italic>Dictyostelium discoideum<\/jats:italic>\n            , indicating that the\nprotein family may modulate intracellular growth in a complex fashion.\nVipD is mildly toxic when overproduced in eukaryotic cells, and the\ntoxicity is partially dependent on the putative phospholipase active\nsite. VipD and its paralogs therefore define a family of translocated\nproteins that may assist in the establishment of a vacuole suitable for\nbacterial replication through functioning as a\nphospholipase.\n          <\/jats:p>","DOI":"10.1128\/iai.02060-05","type":"journal-article","created":{"date-parts":[[2006,5,19]],"date-time":"2006-05-19T23:52:41Z","timestamp":1148082761000},"page":"3597-3606","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":105,"title":["Members of a\n            <i>Legionella pneumophila<\/i>\n            Family of Proteins with ExoU (Phospholipase A) Active Sites Are Translocated to Target Cells"],"prefix":"10.1128","volume":"74","author":[{"given":"Susan M.","family":"VanRheenen","sequence":"first","affiliation":[{"name":"Department\rof Molecular Biology and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Qing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department\rof Molecular Biology and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Department\rof Molecular Biology and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph R.","family":"Isberg","sequence":"additional","affiliation":[{"name":"Department\rof Molecular Biology and Microbiology"},{"name":"Howard Hughes Medical\rInstitute, Tufts University Medical School,\rBoston, Massachusetts 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04539.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb01092.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.7.3029-3034.1998"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.3.751"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04595.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094226"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8914"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03400.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2000.010608.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.3048-3053.2004"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.7.4370-4380.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.12.4021"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.10.4.437-441.1979"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(96)10041-X"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.4891851.x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.162.1.85-91.1985"},{"key":"e_1_3_2_18_2","unstructured":"Harlow E. and D. 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