{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:03:40Z","timestamp":1778605420476,"version":"3.51.4"},"reference-count":31,"publisher":"Microbiology Society","issue":"8","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:p>Neuraminidase A (NanA) is an important virulence factor that is anchored to the pneumococcal cell wall and cleaves sialic acid on host substrates. We noted that a secreted allele of NanA was over-represented in invasive pneumococcal isolates and promoted the development of meningitis when swapped into the genome of non-meningitis isolates replacing cell wall-anchored NanA. Both forms of recombinant NanA directly activated transforming growth factor (TGF)-\u03b2, increased SMAD signalling and promoted loss of endothelial tight junction ZO-1. However, in assays using whole bacteria, only the cell-bound NanA decreased expression of ZO-1 and showed NanA dependence of bacterial invasion of endothelial cells. We conclude that NanA secretion versus retention on the cell surface does not influence neurotropism of clinical isolates. However, we describe a new NanA-TGF-\u03b2 signalling axis that leads to decreased blood-brain barrier integrity and enhances bacterial invasion.<\/jats:p>","DOI":"10.1099\/mic.0.000511","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T14:12:25Z","timestamp":1501164745000},"page":"1198-1207","source":"Crossref","is-referenced-by-count":23,"title":["Pneumococcal neuraminidase activates TGF-\u03b2 signalling"],"prefix":"10.1099","volume":"163","author":[{"given":"Nina","family":"Gratz","sequence":"first","affiliation":[{"name":"Departments of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lip Nam","family":"Loh","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth","family":"Mann","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geli","family":"Gao","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Carter","sequence":"additional","affiliation":[{"name":"Computational Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Rosch","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine I.","family":"Tuomanen","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00008-11"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1086\/424596"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01442-05"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2015.08.005"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1111\/j.2041-1014.2012.00658.x"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1080\/00016480260000111"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1086\/598483"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01251-07"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.07.019"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.7161-7164.2002"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01237-05"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01125-09"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00220-11"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090386"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01490.x"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001136"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00229"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.06.003"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.04.012"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-002-0549-4"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.04.005"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2625"},{"key":"R23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000469069","article-title":"Purification and properties of Streptococcus pneumoniae neuraminidase","volume":"41","author":"Scanlon","year":"1989","journal-title":"Enzyme"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74159"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106591"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.04.016"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1038\/377435a0"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02030-16"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36759"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06425.x"},{"key":"R31","first-page":"528","article-title":"Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction","volume":"8","author":"Horton","year":"1990","journal-title":"Biotechniques"}],"container-title":["Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.000511?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T11:30:56Z","timestamp":1702639856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.000511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,1]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8,1]]}},"URL":"https:\/\/doi.org\/10.1099\/mic.0.000511","relation":{},"ISSN":["1350-0872","1465-2080"],"issn-type":[{"value":"1350-0872","type":"print"},{"value":"1465-2080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,1]]}}}