{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:14:53Z","timestamp":1790406893612,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"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":[[2015,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intracellular pathogens such as\n                    <jats:named-content content-type=\"genus-species\">Shigella flexneri<\/jats:named-content>\n                    and\n                    <jats:named-content content-type=\"genus-species\">Listeria monocytogenes<\/jats:named-content>\n                    achieve dissemination in the intestinal epithelium by displaying actin-based motility in the cytosol of infected cells. As they reach the cell periphery, motile bacteria form plasma membrane protrusions that resolve into vacuoles in adjacent cells, through a poorly understood mechanism. Here, we report on the role of the class II phosphatidylinositol 3-phosphate kinase PIK3C2A in\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    dissemination. Time-lapse microscopy revealed that PIK3C2A was required for the resolution of protrusions into vacuoles through the formation of an intermediate membrane-bound compartment that we refer to as a vacuole-like protrusion (VLP). Genetic rescue of PIK3C2A depletion with RNA interference (RNAi)-resistant cDNA constructs demonstrated that VLP formation required the activity of PIK3C2A in primary infected cells. PIK3C2A expression was required for production of phosphatidylinositol 3-phosphate [PtdIns(3)P] at the plasma membrane surrounding protrusions. PtdIns(3)P production was not observed in the protrusions formed by\n                    <jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>\n                    , whose dissemination did not rely on PIK3C2A. PIK3C2A-mediated PtdIns(3)P production in\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    protrusions was regulated by host cell tyrosine kinase signaling and relied on the integrity of the\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    type 3 secretion system (T3SS). We suggest a model of\n                    <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n                    dissemination in which the formation of VLPs is mediated by the PIK3C2A-dependent production of the signaling lipid PtdIns(3)P in the protrusion membrane, which relies on the T3SS-dependent activation of tyrosine kinase signaling in protrusions.\n                  <\/jats:p>","DOI":"10.1128\/iai.03138-14","type":"journal-article","created":{"date-parts":[[2015,2,10]],"date-time":"2015-02-10T01:36:38Z","timestamp":1423532198000},"page":"1695-1704","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["The Class II Phosphatidylinositol 3-Phosphate Kinase PIK3C2A Promotes Shigella flexneri Dissemination through Formation of Vacuole-Like Protrusions"],"prefix":"10.1128","volume":"83","author":[{"given":"Ana-Maria","family":"Dragoi","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Agaisse","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.54.3.787-792.1986"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90880-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.042308.113331"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2112"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.16.6068"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/357257a0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.10.3463-3471.1991"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.4.1597"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.08.011"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/44183"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/385265a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3739"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80732-1"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.10.3867"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.6.1319"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2002.00185.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05252.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90188-I"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.08.006"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.7.1531"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.3.527"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.6.1333"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.140038"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90358-1"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1021"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12202"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.19.3375"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12051"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600595"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1964"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu546"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00252-09"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02078-14"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.26523"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00853-12"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.03.001"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112738"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.88.5.1503-1518.1964"},{"key":"e_1_3_3_40_2","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.4049\/jimmunol.139.6.2005","article-title":"Adoptive transfer of immunity to Listeria monocytogenes. 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