{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:11:19Z","timestamp":1790813479948,"version":"4.1.0"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"24","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFD1800800; 2021YFD1800404"],"award-info":[{"award-number":["2021YFD1800800; 2021YFD1800404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273009; 31973004"],"award-info":[{"award-number":["32273009; 31973004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["PAPD"],"award-info":[{"award-number":["PAPD"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"&quot;Young Scholars&quot; cultivation program of College of Veterinary Medicine in Nanjing Agricultural University","award":["2012061"],"award-info":[{"award-number":["2012061"]}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["HHMI"],"award-info":[{"award-number":["HHMI"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["RO1-AI-042347"],"award-info":[{"award-number":["RO1-AI-042347"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,6,13]]},"abstract":"<jats:p>\n                    M family proteins are critical virulence determinants of Streptococci.\n                    <jats:italic>Streptococcus equi<\/jats:italic>\n                    subsp.\n                    <jats:italic>zooepidemicus<\/jats:italic>\n                    (SEZ) are Group C streptococci that cause meningitis in animals and humans. SzM, the M protein of SEZ, has been linked to SEZ brain invasion. Here, we demonstrate that SzM is important in SEZ disruption of the blood\u2013brain barrier (BBB). SEZ release SzM-bound membrane vesicles (MVs), and endocytosis of these vesicles by human brain endothelial microvascular cells (hBMECs) results in SzM-dependent cytotoxicity. Furthermore, administration of SzM-bound MVs disrupted the murine BBB. A CRISPR screen revealed that SzM cytotoxicity in hBMECs depends on PTEN-related activation of autophagic cell death. Pharmacologic inhibition of PTEN activity prevented SEZ disruption of the murine BBB and delayed mortality. Our data show that MV delivery of SzM to host cells plays a key role in SEZ pathogenicity and suggests that MV delivery of streptococcal M family proteins is likely a common streptococcal virulence mechanism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2219435120","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T15:16:24Z","timestamp":1685978184000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":23,"title":["Membrane vesicle delivery of a streptococcal M protein disrupts the blood\u2013brain barrier by inducing autophagic endothelial cell death"],"prefix":"10.1073","volume":"120","author":[{"given":"Fei","family":"Pan","sequence":"first","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Zhu","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liang","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchang","family":"Wang","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-0133","authenticated-orcid":false,"given":"Hongjie","family":"Fan","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"},{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-7000","authenticated-orcid":false,"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[{"name":"HHMI, Boston, MA 02115"},{"name":"Brigham and Women\u2019s Hospital Division of Infectious Diseases, Boston, MA 02115"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-5759","authenticated-orcid":false,"given":"Zhe","family":"Ma","sequence":"additional","affiliation":[{"name":"Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China"},{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,6,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000346"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","unstructured":"A. Kerdsin P. Chopjitt R. Hatrongjit P. Boueroy M. Gottschalk Zoonotic infection and clonal dissemination of Streptococcus equi subspecies zooepidemicus sequence type 194 isolated from humans in Thailand. Transbound Emerg Dis. 69 e554\u2013e565 (2021) 10.1111\/tbed.14331.","DOI":"10.1111\/tbed.14331"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","unstructured":"X. Chen Genetic characterization of Streptococcus equi subspecies zooepidemicus associated with high swine mortality in the United States. Transbound Emerg Dis. 67 2797\u20132808 (2020) 10.1111\/tbed.13645.","DOI":"10.1111\/tbed.13645"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2021.109271"},{"key":"e_1_3_4_5_2","first-page":"247","article-title":"Outbreak of Streptococcocus equi Infection in Lampang Province 2011","volume":"38","author":"Ekarakrungreung N.","year":"2012","unstructured":"N. Ekarakrungreung, Outbreak of Streptococcocus equi Infection in Lampang Province 2011. Dis. 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Ma F. Pan M.L. Zhu The CRISPR Screen sequencing raw data. Gene Expression Omnibus database. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE217997. Deposited 15 November 2022."},{"key":"e_1_3_4_66_2","unstructured":"Z. Ma F. Pan The LC\/MS raw data of membrane vesicle. Mendeley Data https:\/\/data.mendeley.com\/datasets\/jc4kj745jw\/1. 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