{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T01:06:13Z","timestamp":1773882373892,"version":"3.50.1"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,1,15]],"date-time":"2017-01-15T00:00:00Z","timestamp":1484438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Transgenic Major Program","award":["2014ZX0800946"],"award-info":[{"award-number":["2014ZX0800946"]}]},{"name":"Special Fund for Agro-scientific Research in Public Interest","award":["201403054"],"award-info":[{"award-number":["201403054"]}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["31272581"],"award-info":[{"award-number":["31272581"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["31672574"],"award-info":[{"award-number":["31672574"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions","award":["PAPD"],"award-info":[{"award-number":["PAPD"]}]},{"DOI":"10.13039\/100007540","name":"Jiangsu Agricultural Science and Technology Innovation Fund","doi-asserted-by":"publisher","award":["CX(15)1056"],"award-info":[{"award-number":["CX(15)1056"]}],"id":[{"id":"10.13039\/100007540","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2017,1,15]]},"abstract":"ABSTRACT<\/jats:title>\n \n The pathogen\n Streptococcus equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n is associated with a wide range of animals, including humans, and outbreaks frequently occur in pigs, equines, and goats. Thus far, few studies have assessed interactions between the host immune system and\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n and how these interactions explain the wide host spectrum of\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n . Neutrophils, the first line of innate immunity, possess a defense mechanism called neutrophil extracellular traps (NETs), which primarily consist of DNA and granule proteins that trap bacteria via charge interactions. Extracellular nucleases play important roles in the degradation of the DNA backbone of NETs. Here, two related extracellular nucleases, nuclease and 5\u2032-nucleotidase (named ENuc and 5Nuc, respectively, in this study), were identified as being encoded by the\n SESEC_RS04165<\/jats:italic>\n gene and the\n SESEC_RS05720<\/jats:italic>\n gene (named\n ENuc<\/jats:italic>\n and\n 5Nuc<\/jats:italic>\n , respectively), and three related gene deletion mutant strains, specifically, the single-mutant\n \u0394ENuc<\/jats:italic>\n and\n \u03945Nuc<\/jats:italic>\n strains and the double-mutant\n \u0394ENuc \u03945Nuc<\/jats:italic>\n strain, were constructed. The\n \u0394ENuc<\/jats:italic>\n and\n \u03945Nuc<\/jats:italic>\n single-mutant strains and the\n \u0394ENuc \u03945Nuc<\/jats:italic>\n double-mutant strain demonstrated lower virulence than wild-type\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n when the mouse survival rate was evaluated postinfection. Furthermore, wild-type\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n more frequently traversed the bloodstream and transferred to other organs. Wild-type\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n induced fewer NETs and was able to survive in NETs, whereas only 40% of the\n \u0394ENuc \u03945Nuc<\/jats:italic>\n double-mutant cells survived.\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n degraded the NET DNA backbone and produced deoxyadenosine, primarily through the action of ENuc and\/or 5Nuc. However, the double-mutant\n \u0394ENuc \u03945Nuc<\/jats:italic>\n strain lost the ability to degrade NETs into deoxyadenosine. Deoxyadenosine decreased RAW 264.7 cell phagocytosis to 40% of that of normal macrophages.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n Streptococcus equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n causes serious bacteremia in its hosts. However, little is known about how\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n interacts with the host innate immune system, particularly innate cells found in the blood.\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n is capable of evading NET-mediated killing via the actions of its potent extracellular nucleases, ENuc and 5Nuc, which directly degrade the NET DNA backbone to deoxyadenosine. In previous studies, other pathogens have required the synergism of nuclease and 5\u2032-nucleotidase to engage in this self-protective process; however, ENuc and 5Nuc both possess nuclease activity and 5\u2032-nucleotidase activity, highlighting the novelty of this discovery. Furthermore, deoxyadenosine impairs phagocytosis but not the intracellular bactericidal activity of macrophages. Here we describe a novel mechanism for\n S. equi<\/jats:named-content>\n subsp.\n zooepidemicus<\/jats:named-content>\n extracellular nucleases in NET degradation, which may provide new insights into the pathogen immune evasion mechanism and the prevention and treatment of bacterial disease.\n <\/jats:p>","DOI":"10.1128\/aem.02468-16","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T02:19:31Z","timestamp":1478312371000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Extracellular Nucleases of Streptococcus equi subsp. zooepidemicus Degrade Neutrophil Extracellular Traps and Impair Macrophage Activity of the Host"],"prefix":"10.1128","volume":"83","author":[{"given":"Fang","family":"Ma","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjie","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China"},{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/2046-0481-66-10"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-377"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000346"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2013.05.006"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.12.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.11.011"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200606027"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201203170"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-171629"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.12.039"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80259-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1242255"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.4.2705"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00378"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.072199-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406641102"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070363"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.6.3523-3534.2000"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.677443"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2091-12-56"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038059"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090097"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2850345"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.545632"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2003.11.003"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01168-13"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1086\/430617"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/plas.2001.1532"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3791\/1724"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2016.02.004"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005043"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu050"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1399004714019725"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.000040"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12578"}],"container-title":["Applied 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