{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:20:20Z","timestamp":1790835620503,"version":"4.1.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T00:00:00Z","timestamp":1524182400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271781"],"award-info":[{"award-number":["81271781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"DOI":"10.3389\/fmicb.2018.00764","type":"journal-article","created":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T12:25:54Z","timestamp":1524227154000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Identification and Characterization of c-di-GMP Metabolic Enzymes of Leptospira interrogans and c-di-GMP Fluctuations After Thermal Shift and Infection"],"prefix":"10.3389","volume":"9","author":[{"given":"Guohui","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongbo","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusi","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinchao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu'ai","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1006\/jmbi.2001.4508","article-title":"Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains","volume":"307","author":"Anantharaman","year":"2001","journal-title":"J. Mol. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/mmi.12447","article-title":"Crystal structure of an HD-GYP domain cyclic-di-GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre","volume":"91","author":"Bellini","year":"2014","journal-title":"Mol. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1099\/mic.0.053892-0","article-title":"A full-length bifunctional protein involved in c-di-GMP turnover is required for long-term survival under nutrient starvation in Mycobacterium smegmatis","volume":"158","author":"Bharati","year":"2012","journal-title":"Microbiology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/S1473-3099(03)00830-2","article-title":"Leptospirosis: a zoonotic disease of global importance","volume":"3","author":"Bharti","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e882","DOI":"10.7717\/peerj.882","article-title":"Cyclic nucleotide binding and structural changes in the isolated GAF domain of anabaena adenylyl cyclase, CyaB2","volume":"3","author":"Biswas","year":"2015","journal-title":"Peerj"},{"key":"B6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.femsle.2005.04.036","article-title":"The phosphodiesterase activity of the HmsP EAL domain is required for negative regulation of biofilm formation in Yersinia pestis","volume":"247","author":"Bobrov","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"B7","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/j.1365-2958.2010.07470.x","article-title":"Systematic analysis of cyclic di-GMP signalling enzymes and their role in biofilm formation and virulence in Yersinia pestis","volume":"79","author":"Bobrov","year":"2011","journal-title":"Mol. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/nature10429","article-title":"STING is a direct innate immune sensor of cyclic di-GMP","volume":"478","author":"Burdette","year":"2011","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/978-3-662-45059-8_3","article-title":"Leptospiral structure, physiology, and metabolism","volume-title":"Leptospira and Leptospirosis","author":"Cameron","year":"2015"},{"key":"B10","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1093\/infdis\/82.3.256","article-title":"Studies on Leptospira Icterohaemorrhagiae: IV. Survival in water and sewage: destruction in water by halogen compounds, synthetic detergents, and heat","volume":"82","author":"Chang","year":"1948","journal-title":"J. Infect. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e0137952","DOI":"10.1371\/journal.pone.0137952","article-title":"Methylatable Signaling helix coordinated inhibitory receiver domain in sensor kinase modulates environmental stress response in Bacillus Cereus","volume":"10","author":"Chen","year":"2015","journal-title":"PLoS ONE"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6657","DOI":"10.1016\/j.bmc.2010.07.068","article-title":"Synthesis of cyclic di-nucleotidic acids as potential inhibitors targeting diguanylate cyclase","volume":"18","author":"Ching","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1128\/JB.00333-15","article-title":"Diversity of cyclic Di-GMP-binding proteins and mechanisms","volume":"198","author":"Chou","year":"2016","journal-title":"J. Bacteriol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"32015","DOI":"10.1074\/jbc.M603589200","article-title":"Allosteric control of cyclic di-GMP signaling","volume":"281","author":"Christen","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"30829","DOI":"10.1074\/jbc.M504429200","article-title":"Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP","volume":"280","author":"Christen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B16","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.2460\/javma.1971.159.11.1477","article-title":"Human infections associated with waterborne Leptospires, and survival studies on serotype pomona","volume":"159","author":"Crawford","year":"1971","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1016\/j.jmb.2017.06.002","article-title":"Structural and enzymatic characterization of a cAMP-dependent diguanylate cyclase from pathogenic Leptospira species","volume":"429","author":"da Costa Vasconcelos","year":"2017","journal-title":"J. Mol. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1101\/gad.502409","article-title":"Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression","volume":"23","author":"Duerig","year":"2009","journal-title":"Genes Dev"},{"key":"B19","first-page":"397","article-title":"In silico discovery and in vitro validation of catechol-containing Sulfonohydrazide compounds as potent inhibitors of the diguanylate cyclase PleD","volume":"198","author":"Fernicola","year":"2015","journal-title":"J. Bacteriol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"6167","DOI":"10.1128\/AEM.01638-14","article-title":"Engineering of Bacillus subtilis strains to allow rapid characterization of heterologous diguanylate cyclases and phosphodiesterases","volume":"80","author":"Gao","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"4782","DOI":"10.1128\/JB.00373-13","article-title":"Functional characterization of core components of the Bacillus subtilis cyclic-Di-GMP signaling pathway","volume":"195","author":"Gao","year":"2013","journal-title":"J. Bacteriol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"W236","DOI":"10.1093\/nar\/gkw370","article-title":"Evolview v2: an online visualization and management tool for customized and annotated phylogenetic trees","volume":"44","author":"He","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.4049\/jimmunol.178.4.2171","article-title":"Bacterial c-di-GMP is an immunostimulatory molecule","volume":"178","author":"Karaolis","year":"2007","journal-title":"J. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1126\/science.1190713","article-title":"An allosteric self-splicing ribozyme triggered by a bacterial second messenger","volume":"329","author":"Lee","year":"2010","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1128\/CMR.14.2.296-326.2001","article-title":"Leptospirosis","volume":"14","author":"Levett","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"B26","first-page":"345","article-title":"Spirochete periplasmic flagella and motility","volume":"2","author":"Li","year":"2000","journal-title":"J. Mol. Microbiol. Biotechnol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"8330","DOI":"10.1038\/ncomms9330","article-title":"Cyclic diguanylate monophosphate directly binds to human siderocalin and inhibits its antibacterial activity","volume":"6","author":"Li","year":"2015","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2T-\u0394\u0394C method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B29","doi-asserted-by":"publisher","first-page":"5848","DOI":"10.1128\/IAI.00755-06","article-title":"Effects of temperature on gene expression patterns in Leptospira interrogans serovar lai as assessed by whole-genome microarrays","volume":"74","author":"Lo","year":"2006","journal-title":"Infect. Immun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1128\/mBio.00163-11","article-title":"The structure of an unconventional HD-GYP protein from Bdellovibrio reveals the roles of conserved residues in this class of cyclic-di-GMP phosphodiesterases","volume":"2","author":"Lovering","year":"2011","journal-title":"MBio"},{"key":"B31","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1128\/IAI.69.1.400-404.2001","article-title":"Temperature-regulated protein synthesis by Leptospira interrogans","volume":"69","author":"Nally","year":"2001","journal-title":"Infect. Immun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"300","DOI":"10.4161\/trns.21903","article-title":"A new way to start: nanoRNA-mediated priming of transcription initiation","volume":"3","author":"Nickels","year":"2012","journal-title":"Transcription"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4676","DOI":"10.1016\/j.vaccine.2008.06.099","article-title":"C-di-GMP is an effective immunomodulator and vaccine adjuvant against pneumococcal infection","volume":"26","author":"Ogunniyi","year":"2008","journal-title":"Vaccine"},{"key":"B34","first-page":"219","article-title":"Some effects of various environmental conditions on the survival of Leptospira pomona","volume":"18","author":"Okazaki","year":"1957","journal-title":"Am. J. Vet. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.micinf.2009.12.004","article-title":"LipL53, a temperature regulated protein from Leptospira interrogans that binds to extracellular matrix molecules","volume":"12","author":"Oliveira","year":"2010","journal-title":"Microbes Infect."},{"key":"B36","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1471-2180-6-51","article-title":"Genome-wide transcriptional analysis of temperature shift in Leptospira interrogans serovar lai strain 56601","volume":"6","author":"Qin","year":"2006","journal-title":"BMC Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3622","DOI":"10.1128\/JB.00165-08","article-title":"Catalytic mechanism of cyclic di-GMP-specific phosphodiesterase: a study of the EAL domain-containing RocR from Pseudomonas aeruginosa","volume":"190","author":"Rao","year":"2008","journal-title":"J. Bacteriol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/MMBR.00043-12","article-title":"Cyclic di-GMP: the first 25 years of a universal bacterial second messenger","volume":"77","author":"R\u00f6mling","year":"2013","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B39","doi-asserted-by":"publisher","first-page":"6712","DOI":"10.1073\/pnas.0600345103","article-title":"Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover","volume":"103","author":"Ryan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B40","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1080\/08927014.2013.832224","article-title":"Identification of small molecules inhibiting diguanylate cyclases to control bacterial biofilm development","volume":"30","author":"Sambanthamoorthy","year":"2014","journal-title":"Biofouling"},{"key":"B41","doi-asserted-by":"publisher","first-page":"5202","DOI":"10.1128\/AAC.01396-12","article-title":"Identification of small molecules that antagonize diguanylate cyclase enzymes to inhibit biofilm formation","volume":"56","author":"Sambanthamoorthy","year":"2012","journal-title":"Antimicrobial Agents Chemother."},{"key":"B42","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.bbapap.2009.09.028","article-title":"Molecular oxygen regulates the enzymatic activity of a heme-containing diguanylate cyclase (HemDGC) for the synthesis of cyclic di-GMP","volume":"1804","author":"Sawai","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1099\/mic.0.024257-0","article-title":"Gene expression patterns and differential input into curli fimbriae regulation of all GGDEF\/EAL domain proteins in Escherichia coli","volume":"155","author":"Sommerfeldt","year":"2009","journal-title":"Microbiology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1110\/ps.072897707","article-title":"DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis","volume":"16","author":"Sousa","year":"2007","journal-title":"Protein Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.mimet.2010.03.020","article-title":"A liquid chromatography-coupled tandem mass spectrometry method for quantitation of cyclic di-guanosine monophosphate","volume":"81","author":"Spangler","year":"2010","journal-title":"J. Microbiol. Methods"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jsb.2015.09.002","article-title":"The REC domain mediated dimerization is critical for FleQ from Pseudomonas aeruginosa to function as a c-di-GMP receptor and flagella gene regulator","volume":"192","author":"Su","year":"2015","journal-title":"J. Struct. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1126\/science.1159519","article-title":"Riboswitches in Eubacteria sense the second messenger cyclic Di-GMP","volume":"321","author":"Sudarsan","year":"2008","journal-title":"Science"},{"key":"B48","doi-asserted-by":"publisher","first-page":"34751","DOI":"10.1074\/jbc.M604819200","article-title":"An unorthodox bacteriophytochrome from Rhodobacter sphaeroides involved in turnover of the second messenger c-di-GMP","volume":"281","author":"Tarutina","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B49","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1128\/MMBR.63.2.479-506.1999","article-title":"PAS domains: internal sensors of oxygen, redox potential, and light","volume":"63","author":"Taylor","year":"1999","journal-title":"Microbiol. Mol. Biol. Rev"},{"key":"B50","doi-asserted-by":"publisher","first-page":"4290","DOI":"10.1111\/1462-2920.12799","article-title":"Temperature affects c-di-GMP signalling and biofilm formation in Vibrio cholerae","volume":"17","author":"Townsley","year":"2015","journal-title":"Environ. Microbiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"9764","DOI":"10.1021\/bi901409g","article-title":"An oxygen-sensing diguanylate cyclase and phosphodiesterase couple for c-di-GMP control","volume":"48","author":"Tuckerman","year":"2009","journal-title":"Biochemistry"},{"key":"B52","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1021\/bi201467c","article-title":"Ultrafast ligand dynamics in the heme-based GAF sensor domains of the histidine kinases DosS and DosT from Mycobacterium tuberculosis","volume":"51","author":"Vos","year":"2012","journal-title":"Biochemistry"},{"key":"B53","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.str.2007.06.016","article-title":"Structure of BeF3- -modified response regulator PleD: implications for diguanylate cyclase activation, catalysis, and feedback inhibition","volume":"15","author":"Wassmann","year":"2007","journal-title":"Structure"},{"key":"B54","doi-asserted-by":"publisher","first-page":"23582","DOI":"10.1074\/jbc.M112.375378","article-title":"Structure of the cytoplasmic region of PelD, a degenerate diguanylate cyclase receptor that regulates exopolysaccharide production in Pseudomonas aeruginosa","volume":"287","author":"Whitney","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"16112","DOI":"10.1074\/jbc.M116.730887","article-title":"A cyclic di-GMP-binding adaptor protein interacts with histidine kinase to regulate two-component signaling","volume":"291","author":"Xu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e857","DOI":"10.1371\/journal.pntd.0000857","article-title":"Transcriptional responses of Leptospira interrogans to host innate immunity: significant changes in metabolism, oxygen tolerance, and outer membrane","volume":"4","author":"Xue","year":"2010","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B57","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1094\/MPMI-12-13-0371-R","article-title":"The degenerate EAL-GGDEF domain protein Filp functions as a cyclic di-GMP receptor and specifically interacts with the PilZ-domain protein PXO_02715 to regulate virulence in Xanthomonas oryzae pv","volume":"27","author":"Yang","year":"2014","journal-title":"oryzae. Mol. Plant Microbe Interact."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1094\/MPMI-01-12-0014-R","article-title":"A novel two-component system PdeK\/PdeR regulates c-di-GMP turnover and virulence of Xanthomonas oryzae pv. oryzae","volume":"25","author":"Yang","year":"2012","journal-title":"Mol. Plant Microbe Interact."},{"key":"B59","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.molcel.2012.05.029","article-title":"Cyclic di-GMP sensing via the innate immune signaling protein STING","volume":"46","author":"Yin","year":"2012","journal-title":"Mol. Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"20871","DOI":"10.1038\/srep20871","article-title":"Characterization of a natural triple-tandem c-di-GMP riboswitch and application of the riboswitch-based dual-fluorescence reporter","volume":"6","author":"Zhou","year":"2016","journal-title":"Sci. Rep."},{"key":"B61","doi-asserted-by":"publisher","first-page":"4396","DOI":"10.1016\/j.bmc.2013.04.050","article-title":"Potent suppression of c-di-GMP synthesis via I-site allosteric inhibition of diguanylate cyclases with 2'-F-c-di-GMP","volume":"21","author":"Zhou","year":"2013","journal-title":"Bioorg. Med. Chem."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fmicb.2018.00764\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T20:14:27Z","timestamp":1751573667000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fmicb.2018.00764\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,20]]},"references-count":61,"alternative-id":["10.3389\/fmicb.2018.00764"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2018.00764","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,20]]},"article-number":"764"}}