{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:30:03Z","timestamp":1790469003438,"version":"4.1.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2015,8,14]],"date-time":"2015-08-14T00:00:00Z","timestamp":1439510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0003952","type":"journal-article","created":{"date-parts":[[2015,8,14]],"date-time":"2015-08-14T18:03:18Z","timestamp":1439575398000},"page":"e0003952","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Role of sph2 Gene Regulation in Hemolytic and Sphingomyelinase Activities Produced by Leptospira interrogans"],"prefix":"10.1371","volume":"9","author":[{"given":"Suneel A.","family":"Narayanavari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristel","family":"Lourdault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjula","family":"Sritharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Haake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Matsunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,8,14]]},"reference":[{"key":"ref1","first-page":"167","article-title":"Zoonosis","author":"M Sritharan","year":"2012"},{"issue":"10","key":"ref2","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrmicro2208","article-title":"<italic>Leptospira<\/italic>: the dawn of the molecular genetics era for an emerging zoonotic pathogen","volume":"7","author":"AI Ko","year":"2009","journal-title":"Nat Rev Microbiol"},{"issue":"6","key":"ref3","doi-asserted-by":"crossref","first-page":"e256","DOI":"10.1371\/journal.pntd.0000256","article-title":"Neglected infections of poverty in the United States of America","volume":"2","author":"PJ Hotez","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S1473-3099(03)00830-2","article-title":"Leptospirosis: a zoonotic disease of global importance","volume":"3","author":"AR Bharti","year":"2003","journal-title":"Lancet Infect Dis"},{"key":"ref5","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"DA Haake","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"ref6","first-page":"393","article-title":"The pathologic anatomy and pathogenesis of fatal human leptospirosis (Weil&apos;s disease)","volume":"40","author":"VM Arean","year":"1962","journal-title":"Am J Pathol"},{"issue":"3","key":"ref7","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.theriogenology.2006.04.016","article-title":"Reproductive losses caused by bovine viral diarrhea virus and leptospirosis","volume":"66","author":"DL Grooms","year":"2006","journal-title":"Theriogenology"},{"issue":"2","key":"ref8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3181\/00379727-91-22214","article-title":"Presence of hemolysin in cultures of pathogenic leptospires","volume":"91","author":"AD Alexander","year":"1956","journal-title":"Proc Soc Exp Biol Med"},{"issue":"6","key":"ref9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.4049\/jimmunol.77.6.405","article-title":"A hemolysin associated with leptospirae","volume":"77","author":"CM Russell","year":"1956","journal-title":"J Immunol"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1099\/00222615-3-1-29","article-title":"Degradation of the erythrocyte phospholipids and haemolysis of the erythrocytes of different animal species by leptospirae","volume":"3","author":"LB Kasarov","year":"1970","journal-title":"J Med Microbiol"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1348-0421.1957.tb00006.x","article-title":"Studies on toxins of pathogenic <italic>Leptospira<\/italic>","volume":"1","author":"S Imamura","year":"1957","journal-title":"Jpn J Microbiol"},{"issue":"8","key":"ref12","doi-asserted-by":"crossref","first-page":"739","DOI":"10.2460\/javma.1975.167.08.739","article-title":"Fatal hemolytic anemia attributed to leptospirosis in lambs","volume":"167","author":"BP Smith","year":"1975","journal-title":"J Am Vet Med Assoc"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.3168\/jds.S0022-0302(76)84339-1","article-title":"Bovine leptospirosis","volume":"59","author":"LE Hanson","year":"1976","journal-title":"J Dairy Sci"},{"issue":"3","key":"ref14","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1080\/00480169.2007.36750","article-title":"Leptospirosis in farmed deer in New Zealand: a review","volume":"55","author":"MA Ayanegui-Alcerreca","year":"2007","journal-title":"N Z Vet J"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1128\/IAI.54.1.262-264.1986","article-title":"Copurification of <italic>Leptospira interrogans<\/italic> serovar pomona hemolysin and sphingomyelinase C","volume":"54","author":"AW Bernheimer","year":"1986","journal-title":"Infect Immun"},{"issue":"8","key":"ref16","doi-asserted-by":"crossref","first-page":"e42266","DOI":"10.1371\/journal.pone.0042266","article-title":"Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-kappaB signaling pathways","volume":"7","author":"H Wang","year":"2012","journal-title":"PloS One"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1128\/IAI.70.1.315-322.2002","article-title":"Cytotoxic activities of <italic>Leptospira interrogans<\/italic> hemolysin SphH as a pore-forming protein on mammalian cells","volume":"70","author":"SH Lee","year":"2002","journal-title":"Infect Immun"},{"issue":"2","key":"ref18","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1128\/IAI.72.2.742-749.2004","article-title":"Host-inducible immunogenic sphingomyelinase-like protein, Lk73.5, of <italic>Leptospira interrogans<\/italic>","volume":"72","author":"S Artiushin","year":"2004","journal-title":"Infect Immun"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.bbrc.2005.06.045","article-title":"Expression and characterization of HlyX hemolysin from <italic>Leptospira interrogans<\/italic> serovar Copenhageni: potentiation of hemolytic activity by LipL32","volume":"333","author":"P Hauk","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000337013","article-title":"Structural Analysis of the Leptospiral sphingomyelinases: <italic>in silico<\/italic> and experimental evaluation of Sph2 as an Mg<sup>++<\/sup>-dependent sphingomyelinase","volume":"22","author":"SA Narayanavari","year":"2012","journal-title":"J Mol Microbiol Biotechnol"},{"issue":"4","key":"ref21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1745-7254.2005.00075.x","article-title":"Identification and classification of all potential hemolysin encoding genes and their products from <italic>Leptospira interrogans<\/italic> serogroup Icterohaemorrhagiae serovar Lai","volume":"26","author":"YX Zhang","year":"2005","journal-title":"Acta Pharmacol Sin"},{"issue":"Pt 5","key":"ref22","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1099\/mic.0.057737-0","article-title":"Multiple leptospiral sphingomyelinases (or are there?)","volume":"158","author":"SA Narayanavari","year":"2012","journal-title":"Microbiology"},{"issue":"2","key":"ref23","doi-asserted-by":"crossref","first-page":"e1607","DOI":"10.1371\/journal.pone.0001607","article-title":"Genome sequence of the saprophyte <italic>Leptospira biflexa<\/italic> provides insights into the evolution of <italic>Leptospira<\/italic> and the pathogenesis of leptospirosis","volume":"3","author":"M Picardeau","year":"2008","journal-title":"PloS One"},{"issue":"24","key":"ref24","doi-asserted-by":"crossref","first-page":"8421","DOI":"10.1128\/JB.01335-06","article-title":"<italic>Staphylococcus aureus<\/italic> IsdB is a hemoglobin receptor required for heme iron utilization","volume":"188","author":"VJ Torres","year":"2006","journal-title":"J Bacteriol"},{"issue":"3","key":"ref25","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1046\/j.1365-2958.2003.03589.x","article-title":"<italic>Leptospira<\/italic> spp. possess a complete haem biosynthetic pathway and are able to use exogenous haem sources","volume":"49","author":"R Guegan","year":"2003","journal-title":"Mol Microbiol"},{"issue":"9","key":"ref26","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1128\/IAI.00324-07","article-title":"Expression and characterization of an iron-regulated hemin-binding protein, HbpA, from <italic>Leptospira interrogans<\/italic> serovar Lai","volume":"75","author":"S Asuthkar","year":"2007","journal-title":"Infect Immun"},{"issue":"7","key":"ref27","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.micinf.2008.04.010","article-title":"<italic>Leptospira interrogans<\/italic> requires a functional heme oxygenase to scavenge iron from hemoglobin","volume":"10","author":"GL Murray","year":"2008","journal-title":"Microbes Infect"},{"issue":"2","key":"ref28","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.micinf.2008.11.014","article-title":"<italic>Leptospira interrogans<\/italic> requires heme oxygenase for disease pathogenesis","volume":"11","author":"GL Murray","year":"2009","journal-title":"Microbes Infect"},{"issue":"2","key":"ref29","first-page":"241","article-title":"Effect of iron deprivation on expression of sphingomyelinase in pathogenic serovar Lai","volume":"10","author":"S Velineni","year":"2009","journal-title":"Online J Bioinform"},{"issue":"2","key":"ref30","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5483\/BMBRep.2008.41.2.119","article-title":"Cytotoxic activity and probable apoptotic effect of Sph2, a sphigomyelinase hemolysin from <italic>Leptospira interrogans<\/italic> strain Lai","volume":"41","author":"YX Zhang","year":"2008","journal-title":"BMB Rep"},{"issue":"22","key":"ref31","doi-asserted-by":"crossref","first-page":"6074","DOI":"10.1128\/JB.01119-12","article-title":"Leptospiral outer membrane protein microarray, a novel approach to identification of host ligand-binding proteins","volume":"194","author":"M Pinne","year":"2012","journal-title":"J Bacteriol"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00284-009-9519-3","article-title":"Evaluation of the expression and protective potential of leptospiral sphingomyelinases","volume":"60","author":"E Carvalho","year":"2010","journal-title":"Curr Microbiol"},{"issue":"6","key":"ref33","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1128\/IAI.01619-06","article-title":"Response of <italic>Leptospira interrogans<\/italic> to physiologic osmolarity: relevance in signaling the environment-to-host transition","volume":"75","author":"J Matsunaga","year":"2007","journal-title":"Infect Immun"},{"issue":"Pt 10","key":"ref34","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1099\/mic.0.2007\/007948-0","article-title":"Osmotic regulation of expression of two extracellular matrix-binding proteins and a haemolysin of <italic>Leptospira interrogans<\/italic>: differential effects on LigA and Sph2 extracellular release","volume":"153","author":"J Matsunaga","year":"2007","journal-title":"Microbiology"},{"issue":"3","key":"ref35","doi-asserted-by":"crossref","first-page":"e1004004","DOI":"10.1371\/journal.ppat.1004004","article-title":"A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by <italic>Leptospira interrogans<\/italic> serovar Copenhageni","volume":"10","author":"MJ Caimano","year":"2014","journal-title":"PLoS Pathog"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1128\/JB.184.2.540-546.2002","article-title":"Molecular cloning and expression of Mn<sup>2+<\/sup>-dependent sphingomyelinase\/hemolysin of an aquatic bacterium, <italic>Pseudomonas<\/italic> sp. strain TK4","volume":"184","author":"N Sueyoshi","year":"2002","journal-title":"J Bacteriol"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1128\/IAI.73.1.70-78.2005","article-title":"Osmolarity, a key environmental signal controlling expression of leptospiral proteins LigA and LigB and the extracellular release of LigA","volume":"73","author":"J Matsunaga","year":"2005","journal-title":"Infect Immun"},{"issue":"2","key":"ref38","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1128\/IAI.01293-08","article-title":"Genome-wide transposon mutagenesis in pathogenic <italic>Leptospira<\/italic> species","volume":"77","author":"GL Murray","year":"2009","journal-title":"Infect Immun"},{"issue":"6","key":"ref39","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1128\/IAI.64.6.2322-2330.1996","article-title":"Molecular cloning and sequence analysis of the gene encoding LipL41, a surface-exposed lipoprotein of pathogenic <italic>Leptospira<\/italic> species","volume":"64","author":"ES Shang","year":"1996","journal-title":"Infect Immun"},{"issue":"16","key":"ref40","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1128\/AEM.00713-12","article-title":"Positive regulation of <italic>Leptospira interrogans kdp<\/italic> expression by KdpE as demonstrated with a novel \u03b2-galactosidase reporter in <italic>Leptospira biflexa<\/italic>","volume":"78","author":"J Matsunaga","year":"2012","journal-title":"Appl Environ Microbiol"},{"issue":"6","key":"ref41","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1128\/IAI.01803-14","article-title":"A putative regulatory genetic locus modulates virulence in the pathogen <italic>Leptospira interrogans<\/italic>","volume":"82","author":"A Eshghi","year":"2014","journal-title":"Infect Immun"},{"issue":"4","key":"ref42","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2<sup>-\u0394\u0394C(T)<\/sup> method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.resmic.2004.09.007","article-title":"A new family of mobilizable suicide plasmids based on broad host range R388 plasmid (IncW) and RP4 plasmid (IncP\u03b1) conjugative machineries and their cognate <italic>Escherichia coli<\/italic> host strains","volume":"156","author":"G Demarre","year":"2005","journal-title":"Res Microbiol"},{"issue":"1","key":"ref44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1128\/AEM.02172-07","article-title":"Conjugative transfer between <italic>Escherichia coli<\/italic> and <italic>Leptospira<\/italic> spp. as a new genetic tool","volume":"74","author":"M Picardeau","year":"2008","journal-title":"Appl Environ Microbiol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-1-61779-603-6_9","article-title":"Construction of a library of random mutants in the spirochete <italic>Leptospira biflexa<\/italic> using a mariner transposon","volume":"859","author":"L Slamti","year":"2012","journal-title":"Methods Mol Biol"},{"key":"ref46","year":"2014"},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1002\/pro.5560051208","article-title":"A distant evolutionary relationship between bacterial sphingomyelinase and mammalian DNase I","volume":"5","author":"Y Matsuo","year":"1996","journal-title":"Protein Sci"},{"issue":"3\u20134","key":"ref48","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.vetmic.2011.02.049","article-title":"A unique genotype of <italic>Leptospira interrogans<\/italic> serovar Pomona type kennewicki is associated with equine abortion","volume":"150","author":"JF Timoney","year":"2011","journal-title":"Vet Microbiol"},{"issue":"7","key":"ref49","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/mim.1982.26.7.547","article-title":"Hemolytic activity of <italic>Leptospira interrogans<\/italic> serovar canicola cultured in protein-free medium","volume":"26","author":"Y Yanagihara","year":"1982","journal-title":"Microbiol Immunol"},{"issue":"3","key":"ref50","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1348-0421.1984.tb00681.x","article-title":"Characterization of inhibitor to leptospiral hemolysin present in bovine serum","volume":"28","author":"T Kojima","year":"1984","journal-title":"Microbiol Immunol"},{"issue":"7","key":"ref51","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1128\/IAI.58.7.2177-2185.1990","article-title":"Molecular analysis of a sphingomyelinase C gene from <italic>Leptospira interrogans<\/italic> serovar hardjo","volume":"58","author":"RP Segers","year":"1990","journal-title":"Infect Immun"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0003952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:32:38Z","timestamp":1748565158000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0003952"}},"subtitle":[],"editor":[{"given":"Mathieu","family":"Picardeau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,8,14]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2015,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0003952","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,14]]}}}