{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:39:01Z","timestamp":1790282341486,"version":"4.1.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:00:00Z","timestamp":1533254400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST104-2320-B006-049"],"award-info":[{"award-number":["MOST104-2320-B006-049"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST105-2320-B006-009"],"award-info":[{"award-number":["MOST105-2320-B006-009"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST106-2320-B010-039"],"award-info":[{"award-number":["MOST106-2320-B010-039"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"DOI":"10.3389\/fmicb.2018.01733","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:36:37Z","timestamp":1533256597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["NAD-Glycohydrolase Depletes Intracellular NAD+ and Inhibits Acidification of Autophagosomes to Enhance Multiplication of Group A Streptococcus in Endothelial Cells"],"prefix":"10.3389","volume":"9","author":[{"given":"Cheng-Lu","family":"Hsieh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsuan-Min","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ying","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Xing","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Shin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Chiang-Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Jane","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Chuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiunn-Jong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1093\/jb\/mvj162","article-title":"Autophagy in innate immunity against intracellular bacteria.","volume":"140","author":"Amano","year":"2006","journal-title":"J. Biochem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1111\/j.1462-5822.2011.01610.x","article-title":"The FbaB-type fibronectin-binding protein of Streptococcus pyogenes promotes specific invasion into endothelial cells.","volume":"13","author":"Amelung","year":"2011","journal-title":"Cell. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1111\/cmi.12531","article-title":"Streptococcal toxins: role in pathogenesis and disease.","volume":"17","author":"Barnett","year":"2015","journal-title":"Cell. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.chom.2013.11.003","article-title":"The globally disseminated M1T1 clone of group A Streptococcus evades autophagy for intracellular replication.","volume":"14","author":"Barnett","year":"2013","journal-title":"Cell Host Microbe"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01690-14","article-title":"Streptolysin O and NAD-glycohydrolase prevent phagolysosome acidification and promote group A Streptococcus survival in macrophages.","volume":"5","author":"Bastiat-Sempe","year":"2014","journal-title":"mBio"},{"key":"B6","doi-asserted-by":"publisher","first-page":"6562","DOI":"10.1128\/IAI.73.10.6562-6566.2005","article-title":"Role of NADase in virulence in experimental invasive group A streptococcal infection.","volume":"73","author":"Bricker","year":"2005","journal-title":"Infect. Immun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1046\/j.1365-2958.2002.02876.x","article-title":"NAD+-glycohydrolase acts as an intracellular toxin to enhance the extracellular survival of group A streptococci.","volume":"44","author":"Bricker","year":"2002","journal-title":"Mol. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.cmet.2015.05.023","article-title":"NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus.","volume":"22","author":"Canto","year":"2015","journal-title":"Cell Metab."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1111\/cmi.12442","article-title":"The Streptococcus pyogenes NAD+ glycohydrolase modulates epithelial cell PARylation and HMGB1 release.","volume":"17","author":"Chandrasekaran","year":"2015","journal-title":"Cell. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02215-15","article-title":"The NADase-negative variant of the Streptococcus pyogenes toxin NAD+ glycohydrolase induces JNK1-mediated programmed cellular necrosis.","volume":"7","author":"Chandrasekaran","year":"2016","journal-title":"mBio"},{"key":"B11","doi-asserted-by":"publisher","first-page":"20064","DOI":"10.1074\/jbc.M113.481556","article-title":"Analysis of polymorphic residues reveals distinct enzymatic and cytotoxic activities of the Streptococcus pyogenes NAD+ glycohydrolase.","volume":"288","author":"Chandrasekaran","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01935","article-title":"Repression of Rgg but not upregulation of LacD.1 in emm1-type covS mutant mediates the SpeB repression in group A Streptococcus.","volume":"7","author":"Chiang-Ni","year":"2016","journal-title":"Front. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01422-17","article-title":"Population and whole genome sequence based characterization of invasive group A streptococci recovered in the United States during 2015.","volume":"8","author":"Chochua","year":"2017","journal-title":"mBio"},{"key":"B14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-0-387-73960-1_3","article-title":"Pathogenesis of group A streptococcal infections and their sequelae.","volume":"609","author":"Cunningham","year":"2008","journal-title":"Adv. Exp. Med. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/nri3532","article-title":"Autophagy in infection, inflammation and immunity.","volume":"13","author":"Deretic","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5683","DOI":"10.1074\/jbc.M109.070300","article-title":"Characterization of Streptococcus pyogenes \u03b2-NAD+ glycohydrolase: re-evaluation of enzymatic properties associated with pathogenesis.","volume":"285","author":"Ghosh","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00756-17","article-title":"Inhibition of inflammasome-dependent interleukin 1\u03b2 production by streptococcal NAD+-glycohydrolase: evidence for extracellular activity.","volume":"8","author":"Hancz","year":"2017","journal-title":"mBio"},{"key":"B18","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/978-3-642-00302-8_9","article-title":"Autophagy in immunity against intracellular bacteria.","volume":"335","author":"Huang","year":"2009","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrmicro3160","article-title":"Bacteria-autophagy interplay: a battle for survival.","volume":"12","author":"Huang","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1086\/508773","article-title":"Reduced ability of penicillin to eradicate ingested group A streptococci from epithelial cells: clinical and pathogenetic implications.","volume":"43","author":"Kaplan","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"9181","DOI":"10.1074\/jbc.M506879200","article-title":"Genetic and biochemical properties of streptococcal NAD-glycohydrolase inhibitor.","volume":"281","author":"Kimoto","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.bbaexp.2004.10.011","article-title":"Molecular characterization of NADase-streptolysin O operon of hemolytic streptococci.","volume":"1681","author":"Kimoto","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"B24","doi-asserted-by":"publisher","first-page":"12115","DOI":"10.1073\/pnas.91.25.12115","article-title":"Group A streptococci efficiently invade human respiratory epithelial cells.","volume":"91","author":"LaPenta","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B25","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1097\/MOH.0b013e328345a3d1","article-title":"Endothelial activation, dysfunction and permeability during severe infections.","volume":"18","author":"Lee","year":"2011","journal-title":"Curr. Opin. Hematol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00332-10","article-title":"Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus.","volume":"2","author":"Logsdon","year":"2011","journal-title":"mBio"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01435-15","article-title":"Insufficient acidification of autophagosomes facilitates group A Streptococcus survival and growth in endothelial cells.","volume":"6","author":"Lu","year":"2015","journal-title":"mBio"},{"key":"B28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0092-8674(01)00198-2","article-title":"Cytolysin-mediated translocation (CMT): a functional equivalent of type III secretion in gram-positive bacteria.","volume":"104","author":"Madden","year":"2001","journal-title":"Cell"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0010035","article-title":"A novel endogenous inhibitor of the secreted streptococcal NAD-glycohydrolase.","volume":"1","author":"Meehl","year":"2005","journal-title":"PLoS Pathog."},{"key":"B30","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/cr.2010.82","article-title":"Overview of macroautophagy regulation in mammalian cells.","volume":"20","author":"Mehrpour","year":"2010","journal-title":"Cell Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1007\/s00018-015-2119-4","article-title":"Exploring NAD+ metabolism in host-pathogen interactions.","volume":"73","author":"Mesquita","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"8216","DOI":"10.1074\/jbc.M511674200","article-title":"Enhancement of streptolysin O activity and intrinsic cytotoxic effects of the group A streptococcal toxin, NAD-glycohydrolase.","volume":"281","author":"Michos","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"61","DOI":"10.4161\/auto.5.1.7272","article-title":"PARP-1 is involved in autophagy induced by DNA damage.","volume":"5","author":"Munoz-Gamez","year":"2009","journal-title":"Autophagy"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1126\/science.1103966","article-title":"Autophagy defends cells against invading group A Streptococcus.","volume":"306","author":"Nakagawa","year":"2004","journal-title":"Science"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1002\/jcp.24399","article-title":"Sirtuins\u2019 modulation of autophagy.","volume":"228","author":"Ng","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1111\/j.1462-5822.2012.01792.x","article-title":"The small GTPases Rab9A and Rab23 function at distinct steps in autophagy during group A Streptococcus infection.","volume":"14","author":"Nozawa","year":"2012","journal-title":"Cell. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1159\/000358085","article-title":"The M1 protein of Streptococcus pyogenes triggers an innate uptake mechanism into polarized human endothelial cells.","volume":"6","author":"Ochel","year":"2014","journal-title":"J. Innate Immun."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003394","article-title":"Streptolysin O and its co-toxin NAD-glycohydrolase protect group A Streptococcus from xenophagic killing.","volume":"9","author":"O\u2019Seaghdha","year":"2013","journal-title":"PLoS Pathog."},{"key":"B39","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1097\/00005537-199705000-00016","article-title":"Intracellular reservoir of Streptococcus pyogenes in vivo: a possible explanation for recurrent pharyngotonsillitis.","volume":"107","author":"Osterlund","year":"1997","journal-title":"Laryngoscope"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00054","article-title":"Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.","volume":"3","author":"Pareja","year":"2013","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR.","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"22666","DOI":"10.1074\/jbc.M109.100131","article-title":"Specific behavior of intracellular Streptococcus pyogenes that has undergone autophagic degradation is associated with bacterial streptolysin O and host small G proteins Rab5 and Rab7.","volume":"285","author":"Sakurai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.mib.2010.11.001","article-title":"Mechanisms and consequences of bacterial targeting by the autophagy pathway.","volume":"14","author":"Shahnazari","year":"2011","journal-title":"Curr. Opin. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005468","article-title":"NAD+-glycohydrolase promotes intracellular survival of group A Streptococcus.","volume":"12","author":"Sharma","year":"2016","journal-title":"PLoS Pathog."},{"key":"B45","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1128\/IAI.71.1.446-455.2003","article-title":"Cytotoxic effects of streptolysin O and streptolysin S enhance the virulence of poorly encapsulated group A streptococci.","volume":"71","author":"Sierig","year":"2003","journal-title":"Infect. Immun."},{"key":"B46","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/nsmb.3064","article-title":"The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.","volume":"22","author":"Sun","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00622-15","article-title":"Emergence of a new highly successful acapsular group A Streptococcus clade of genotype emm89 in the United Kingdom.","volume":"6","author":"Turner","year":"2015","journal-title":"mBio"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01382-17","article-title":"Binding of NAD+-glycohydrolase to streptolysin O stabilizes both toxins and promotes virulence of group A Streptococcus.","volume":"8","author":"Velarde","year":"2017","journal-title":"mBio"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081882","article-title":"Peroxide responsive regulator PerR of group A Streptococcus is required for the expression of phage-associated DNase Sda1 under oxidative stress.","volume":"8","author":"Wang","year":"2013","journal-title":"PLoS One"},{"key":"B50","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.immuni.2005.09.007","article-title":"Phagosome maturation proceeds independently of stimulation of toll-like receptors 2 and 4.","volume":"23","author":"Yates","year":"2005","journal-title":"Immunity"},{"key":"B51","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.metabol.2015.11.010","article-title":"The potential regulatory roles of NAD+ and its metabolism in autophagy.","volume":"65","author":"Zhang","year":"2016","journal-title":"Metabolism"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.00149-12","article-title":"Complete genome sequence of emm1 Streptococcus pyogenes A 20, a strain with an intact two-component system, CovRS, isolated from a patient with necrotizing fasciitis.","volume":"1","author":"Zheng","year":"2013","journal-title":"Genome Announc."},{"key":"B53","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.1172\/JCI82478","article-title":"A molecular trigger for intercontinental epidemics of group A Streptococcus.","volume":"125","author":"Zhu","year":"","journal-title":"J. Clin. Invest."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01378-15","article-title":"Trading capsule for increased cytotoxin production: contribution to virulence of a newly emerged clade of emm89 Streptococcus pyogenes.","volume":"6","author":"Zhu","year":"","journal-title":"mBio"},{"key":"B55","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.ajpath.2016.11.003","article-title":"Contribution of secreted NADase and streptolysin O to the pathogenesis of epidemic serotype M1 Streptococcus pyogenes infections.","volume":"187","author":"Zhu","year":"2016","journal-title":"Am. J. Pathol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2018.01733\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:36:41Z","timestamp":1533256601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2018.01733\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,3]]},"references-count":55,"alternative-id":["10.3389\/fmicb.2018.01733"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2018.01733","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,3]]},"article-number":"1733"}}