{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:23:02Z","timestamp":1789762982758,"version":"4.0.1"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["K12GM074869, 1SC2GM141988-01"],"award-info":[{"award-number":["K12GM074869, 1SC2GM141988-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["5R37AI037657"],"award-info":[{"award-number":["5R37AI037657"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2023,9,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Streptococcus pneumoniae,<\/jats:italic>\n            a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis.\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration\n            <jats:italic>in vitro<\/jats:italic>\n            and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation. Reducing the MOI to 2 decreased PMN recruitment two-fold and preserved the monolayer, but apical-to-basolateral translocation of\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            remained relatively efficient. At both MOI of 2 and 20, PLY was required for maximal PMN recruitment and bacterial translocation. Co-infection by wild-type\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            restored translocation by a PLY-deficient mutant, indicating that PLY can act in\n            <jats:italic>trans<\/jats:italic>\n            . Investigating the contribution of\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            infection on apical junction complexes in the absence of PMN transmigration, we found that\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            infection triggered the cleavage and mislocalization of the adherens junction (AJ) protein E-cadherin. This disruption was PLY-dependent at MOI of 2 and was recapitulated by purified PLY, requiring its pore-forming activity. In contrast, at MOI of 20, E-cadherin disruption was independent of PLY, indicating that\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            encodes multiple means to disrupt epithelial integrity. This disruption was insufficient to promote bacterial translocation in the absence of PMNs. Thus,\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            triggers cleavage and mislocalization of E-cadherin through PLY-dependent and -independent mechanisms, but maximal bacterial translocation across epithelial monolayers requires PLY-dependent neutrophil transmigration.\n          <\/jats:p>","DOI":"10.1128\/iai.00213-23","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T13:01:43Z","timestamp":1692622903000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Pore-forming activity of\n            <i>S. pneumoniae<\/i>\n            pneumolysin disrupts the paracellular localization of the epithelial adherens junction protein E-cadherin"],"prefix":"10.1128","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4572-8663","authenticated-orcid":true,"given":"Shuying","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, Massachusetts, USA"},{"name":"Program in Immunology, Tufts Graduate School of Biomedical Sciences , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devons","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, San Jose State University , San Jose, California, USA"},{"name":"Department of Microbiology and Environmental Toxicology, University of California , Santa Cruz, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Z.","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, San Jose State University , San Jose, California, USA"},{"name":"Department of Microbiology and Environmental Toxicology, University of California , Santa Cruz, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, Massachusetts, USA"},{"name":"University of Puerto Rico , Cayey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, Massachusetts, USA"},{"name":"Francisco de Vitoria University , Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumin","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney K.","family":"Tweten","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Leong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, Massachusetts, USA"},{"name":"Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance at Tufts (Levy CIMAR) , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2979-1382","authenticated-orcid":true,"given":"Walter","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University , Boston, Massachusetts, USA"},{"name":"Department of Biological Sciences, San Jose State University , San Jose, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"CDC\n. 2019. Pneumococcal disease. Available from: https:\/\/www.cdc.gov\/pneumococcal\/index.html. Retrieved 18 May 2019."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91234-y"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.4161\/tisb.24997"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-017-1551-y"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.08.004"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/15419061.2013.854778"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.05.049"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-016-1917-3"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.04.012"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003727"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608213104"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10100387"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.442-447.1995"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15751-6"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.000511"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010215"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001533"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00333.2005"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/341563"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800748"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300522"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005126"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2737-2"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.01.056"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00857.x"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22401"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-016-0449-x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20011804"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2013-000014"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500124"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00280-17"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.1.119"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1997.0150"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73454-w"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01543"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0280-x"},{"key":"e_1_3_4_38_2","volume-title":"Streptococcus pneumoniae: molecular mechanisms of host-pathogen interactions","author":"Neill DRM","year":"2015","unstructured":"Neill DRM , Timothy J , Kadioglu A . 2015. Streptococcus pneumoniae: molecular mechanisms of host-pathogen interactions. Academic Press, Amsterdam."},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117631"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3791\/50823"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5712"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi981452f"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.131.6.1599"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.865528"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2016.07.022"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02598"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep38013"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2451"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031259"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006579"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911581107"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183237"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00184-08"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.4.1352-1358.1993"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2061336"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807631200"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10060234"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.09.005"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200708010"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009432"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.11.034"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-01-0014"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00160"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.4776"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0047TR"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00199"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1159\/000073962"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0091-6749(95)70322-5"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1080\/01902140701198500"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-3273"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00213-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00213-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T14:31:28Z","timestamp":1694701888000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00213-23"}},"subtitle":[],"editor":[{"given":"Kimberly A.","family":"Kline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":69,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9,14]]}},"alternative-id":["10.1128\/iai.00213-23"],"URL":"https:\/\/doi.org\/10.1128\/iai.00213-23","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]},"assertion":[{"value":"2023-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00213-23"}}