{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T07:13:23Z","timestamp":1766819603622},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Catabolite control protein A (CcpA) is a highly conserved, master regulator of carbon source utilization in gram-positive bacteria, but the CcpA regulon remains ill-defined. In this study we aimed to clarify the CcpA regulon by determining the impact of CcpA-inactivation on the virulence and transcriptome of three distinct serotypes of the major human pathogen Group A<jats:italic>Streptococcus<\/jats:italic>(GAS). CcpA-inactivation significantly decreased GAS virulence in a broad array of animal challenge models consistent with the idea that CcpA is critical to gram-positive bacterial pathogenesis. Via comparative transcriptomics, we established that the GAS CcpA core regulon is enriched for highly conserved CcpA binding motifs (i.e.<jats:italic>cre<\/jats:italic>sites). Conversely, strain-specific differences in the CcpA transcriptome seems to consist primarily of affected secondary networks. Refinement of<jats:italic>cre<\/jats:italic>site composition via analysis of the core regulon facilitated development of a modified<jats:italic>cre<\/jats:italic>consensus that shows promise for improved prediction of CcpA targets in other medically relevant gram-positive pathogens.<\/jats:p>","DOI":"10.1038\/srep32442","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T10:35:09Z","timestamp":1472726109000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Multi-Serotype Approach Clarifies the Catabolite Control Protein A Regulon in the Major Human Pathogen Group A Streptococcus"],"prefix":"10.1038","volume":"6","author":[{"given":"Sruti","family":"DebRoy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Salda\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante","family":"Travisany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Montano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Galloway-Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Horstmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Maass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio","family":"Latorre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel A.","family":"Shelburne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"BFsrep32442_CR1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/nature11623","volume":"492","author":"AR Pacheco","year":"2012","unstructured":"Pacheco, A. R. et al. Fucose sensing regulates bacterial intestinal colonization. Nature 492, 113\u2013117 (2012).","journal-title":"Nature"},{"key":"BFsrep32442_CR2","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/nrmicro2351","volume":"8","author":"W Eisenreich","year":"2010","unstructured":"Eisenreich, W., Dandekar, T., Heesemann, J. & Goebel, W. Carbon metabolism of intracellular bacterial pathogens and possible links to virulence. Nat Rev Microbiol 8, 401\u2013412 (2010).","journal-title":"Nat Rev Microbiol"},{"key":"BFsrep32442_CR3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.tim.2011.04.003","volume":"19","author":"L Rohmer","year":"2011","unstructured":"Rohmer, L., Hocquet, D. & Miller, S. I. Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis. Trends Microbiol 19, 341\u2013348 (2011).","journal-title":"Trends Microbiol"},{"key":"BFsrep32442_CR4","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3389\/fmicb.2015.00402","volume":"6","author":"F Santos-Beneit","year":"2015","unstructured":"Santos-Beneit, F. The Pho regulon: a huge regulatory network in bacteria. Front Microbiol 6, 402 (2015).","journal-title":"Front Microbiol"},{"key":"BFsrep32442_CR5","doi-asserted-by":"publisher","first-page":"5414","DOI":"10.1038\/sj.emboj.7601393","volume":"25","author":"JA Loughman","year":"2006","unstructured":"Loughman, J. A. & Caparon, M. G. A novel adaptation of aldolase regulates virulence in Streptococcus pyogenes. Embo J 25, 5414\u20135422 (2006).","journal-title":"Embo J"},{"key":"BFsrep32442_CR6","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1146\/annurev.biochem.69.1.183","volume":"69","author":"AM Stock","year":"2000","unstructured":"Stock, A. M., Robinson, V. L. & Goudreau, P. N. Two-component signal transduction. Annu Rev Biochem 69, 183\u2013215 (2000).","journal-title":"Annu Rev Biochem"},{"key":"BFsrep32442_CR7","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nm1252","volume":"11","author":"EJ Munoz-Elias","year":"2005","unstructured":"Munoz-Elias, E. J. & McKinney, J. D. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med 11, 638\u2013644 (2005).","journal-title":"Nat Med"},{"key":"BFsrep32442_CR8","doi-asserted-by":"publisher","first-page":"927","DOI":"10.2353\/ajpath.2006.060112","volume":"169","author":"MR Graham","year":"2006","unstructured":"Graham, M. R. et al. Analysis of the transcriptome of group A Streptococcus in mouse soft tissue infection. Am J Pathol 169, 927\u2013942 (2006).","journal-title":"Am J Pathol"},{"key":"BFsrep32442_CR9","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1046\/j.1365-2958.2000.02099.x","volume":"37","author":"AL Jones","year":"2000","unstructured":"Jones, A. L., Knoll, K. M. & Rubens, C. E. Identification of Streptococcus agalactiae virulence genes in the neonatal rat sepsis model using signature-tagged mutagenesis. Mol Microbiol 37, 1444\u20131455 (2000).","journal-title":"Mol Microbiol"},{"key":"BFsrep32442_CR10","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nrmicro1772","volume":"5","author":"AL Sonenshein","year":"2007","unstructured":"Sonenshein, A. L. Control of key metabolic intersections in Bacillus subtilis. Nat Rev Microbiol 5, 917\u2013927 (2007).","journal-title":"Nat Rev Microbiol"},{"key":"BFsrep32442_CR11","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1128\/MMBR.67.4.475-490.2003","volume":"67","author":"JB Warner","year":"2003","unstructured":"Warner, J. B. & Lolkema, J. S. CcpA-dependent carbon catabolite repression in bacteria. Microbiol Mol Biol Rev 67, 475\u2013490 (2003).","journal-title":"Microbiol Mol Biol Rev"},{"key":"BFsrep32442_CR12","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cell.2004.08.027","volume":"118","author":"MA Schumacher","year":"2004","unstructured":"Schumacher, M. A. et al. Structural basis for allosteric control of the transcription regulator CcpA by the phosphoprotein HPr-Ser46-P. Cell 118, 731\u2013741 (2004).","journal-title":"Cell"},{"key":"BFsrep32442_CR13","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.bbapap.2005.07.029","volume":"1754","author":"J Deutscher","year":"2005","unstructured":"Deutscher, J., Herro, R., Bourand, A., Mijakovic, I. & Poncet, S. P-Ser-HPr\u2013a link between carbon metabolism and the virulence of some pathogenic bacteria. Biochim Biophys Acta 1754, 118\u2013125 (2005).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep32442_CR14","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1128\/MMBR.00024-06","volume":"70","author":"J Deutscher","year":"2006","unstructured":"Deutscher, J., Francke, C. & Postma, P. W. How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol Mol Biol Rev 70, 939\u20131031 (2006).","journal-title":"Microbiol Mol Biol Rev"},{"key":"BFsrep32442_CR15","doi-asserted-by":"publisher","first-page":"8340","DOI":"10.1128\/JB.187.24.8340-8349.2005","volume":"187","author":"R Iyer","year":"2005","unstructured":"Iyer, R., Baliga, N. S. & Camilli, A. Catabolite control protein A (CcpA) contributes to virulence and regulation of sugar metabolism in Streptococcus pneumoniae. J Bacteriol 187, 8340\u20138349 (2005).","journal-title":"J Bacteriol"},{"key":"BFsrep32442_CR16","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1073\/pnas.0711767105","volume":"105","author":"SA Shelburne 3rd","year":"2008","unstructured":"Shelburne, S. A. 3rd et al. A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus. Proc Natl Acad Sci USA 105, 1698\u20131703 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep32442_CR17","doi-asserted-by":"crossref","unstructured":"Kietzman, C. C. & Caparon, M. G. CcpA and LacD.1 affect temporal regulation of S. pyogenes virulence genes. Infect Immun (2009).","DOI":"10.1128\/IAI.00746-09"},{"key":"BFsrep32442_CR18","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1099\/mic.0.046417-0","volume":"157","author":"J Willenborg","year":"2011","unstructured":"Willenborg, J. et al. Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis. Microbiology 157, 1823\u20131833 (2011).","journal-title":"Microbiology"},{"key":"BFsrep32442_CR19","doi-asserted-by":"publisher","first-page":"3580","DOI":"10.1128\/IAI.01911-14","volume":"82","author":"SR Somarajan","year":"2014","unstructured":"Somarajan, S. R., Roh, J. H., Singh, K. V., Weinstock, G. M. & Murray, B. E. CcpA is important for growth and virulence of Enterococcus faecium. Infect Immun 82, 3580\u20133587 (2014).","journal-title":"Infect Immun"},{"key":"BFsrep32442_CR20","doi-asserted-by":"publisher","first-page":"e60465","DOI":"10.1371\/journal.pone.0060465","volume":"8","author":"L Zeng","year":"2013","unstructured":"Zeng, L. et al. Gene regulation by CcpA and catabolite repression explored by RNA-Seq in Streptococcus mutans. PLoS One 8, e60465 (2013).","journal-title":"PLoS One"},{"key":"BFsrep32442_CR21","doi-asserted-by":"publisher","first-page":"10701","DOI":"10.1093\/nar\/gks864","volume":"40","author":"A Antunes","year":"2012","unstructured":"Antunes, A. et al. Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile. Nucleic Acids Res 40, 10701\u201310718 (2012).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep32442_CR22","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1128\/JB.00972-06","volume":"189","author":"S Mertins","year":"2007","unstructured":"Mertins, S. et al. Interference of components of the phosphoenolpyruvate phosphotransferase system with the central virulence gene regulator PrfA of Listeria monocytogenes. J Bacteriol 189, 473\u2013490 (2007).","journal-title":"J Bacteriol"},{"key":"BFsrep32442_CR23","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1128\/JB.01656-09","volume":"193","author":"C Chiang","year":"2011","unstructured":"Chiang, C., Bongiorni, C. & Perego, M. Glucose-dependent activation of Bacillus anthracis toxin gene expression and virulence requires the carbon catabolite protein CcpA. J Bacteriol 193, 52\u201362 (2011).","journal-title":"J Bacteriol"},{"key":"BFsrep32442_CR24","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.micpath.2011.10.008","volume":"52","author":"MB Mendez","year":"2012","unstructured":"Mendez, M. B., Goni, A., Ramirez, W. & Grau, R. R. Sugar inhibits the production of the toxins that trigger clostridial gas gangrene. Microb Pathog 52, 85\u201391 (2012).","journal-title":"Microb Pathog"},{"key":"BFsrep32442_CR25","doi-asserted-by":"publisher","first-page":"8405","DOI":"10.1128\/JB.01038-07","volume":"189","author":"AC Almengor","year":"2007","unstructured":"Almengor, A. C., Kinkel, T. L., Day, S. J. & McIver, K. S. The catabolite control protein CcpA binds to Pmga and influences expression of the virulence regulator Mga in the group A Streptococcus. J Bacteriol 189, 8405\u20138416 (2007).","journal-title":"J Bacteriol"},{"key":"BFsrep32442_CR26","doi-asserted-by":"publisher","first-page":"S331","DOI":"10.1093\/cid\/ciu598","volume":"59","author":"T Holland","year":"2014","unstructured":"Holland, T., Fowler, V. G. Jr. & Shelburne, S. A. 3rd. Invasive gram-positive bacterial infection in cancer patients. Clin Infect Dis 59, Suppl 5, S331\u2013S334 (2014).","journal-title":"Clin Infect Dis"},{"key":"BFsrep32442_CR27","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/1471-2180-9-95","volume":"9","author":"K Seidl","year":"2009","unstructured":"Seidl, K. et al. Effect of a glucose impulse on the CcpA regulon in Staphylococcus aureus. BMC Microbiol 9, 95 (2009).","journal-title":"BMC Microbiol"},{"key":"BFsrep32442_CR28","unstructured":"Efstratiou, A. & Lamagni, T. Epidemiology of Streptococcus pyogenes. In Streptococcus pyogenes: Basic Biology to Clinical Manifestations (eds. Ferretti, J. J., Stevens, D. L. & Fischetti, V. A. ) (Oklahoma City (OK), 2016)."},{"key":"BFsrep32442_CR29","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.bbapap.2005.07.042","volume":"1754","author":"S Nessler","year":"2005","unstructured":"Nessler, S. The bacterial HPr kinase\/phosphorylase: a new type of Ser\/Thr kinase as antimicrobial target. Biochim Biophys Acta 1754, 126\u2013131 (2005).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep32442_CR30","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1128\/AAC.50.4.1183-1194.2006","volume":"50","author":"K Seidl","year":"2006","unstructured":"Seidl, K. et al. Staphylococcus aureus CcpA affects virulence determinant production and antibiotic resistance. Antimicrob Agents Chemother 50, 1183\u20131194 (2006).","journal-title":"Antimicrob Agents Chemother"},{"key":"BFsrep32442_CR31","doi-asserted-by":"publisher","first-page":"e26707","DOI":"10.1371\/journal.pone.0026707","volume":"6","author":"SM Carvalho","year":"2011","unstructured":"Carvalho, S. M., Kloosterman, T. G., Kuipers, O. P. & Neves, A. R. CcpA ensures optimal metabolic fitness of Streptococcus pneumoniae. PLoS One 6, e26707 (2011).","journal-title":"PLoS One"},{"key":"BFsrep32442_CR32","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.tim.2007.05.001","volume":"15","author":"AH Tart","year":"2007","unstructured":"Tart, A. H., Walker, M. J. & Musser, J. M. New understanding of the group A Streptococcus pathogenesis cycle. Trends Microbiol 15, 318\u2013325 (2007).","journal-title":"Trends Microbiol"},{"key":"BFsrep32442_CR33","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1111\/j.1365-2958.2006.05381.x","volume":"62","author":"DA Ribardo","year":"2006","unstructured":"Ribardo, D. A. & McIver, K. S. Defining the Mga regulon: Comparative transcriptome analysis reveals both direct and indirect regulation by Mga in the group A Streptococcus. Mol Microbiol 62, 491\u2013508 (2006).","journal-title":"Mol Microbiol"},{"key":"BFsrep32442_CR34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1574-6968.2008.01171.x","volume":"284","author":"AV Dmitriev","year":"2008","unstructured":"Dmitriev, A. V., McDowell, E. J. & Chaussee, M. S. Inter- and intraserotypic variation in the Streptococcus pyogenes Rgg regulon. FEMS Microbiol Lett 284, 43\u201351 (2008).","journal-title":"FEMS Microbiol Lett"},{"key":"BFsrep32442_CR35","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/S1473-3099(09)70178-1","volume":"9","author":"AC Steer","year":"2009","unstructured":"Steer, A. C., Law, I., Matatolu, L., Beall, B. W. & Carapetis, J. R. Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis 9, 611\u2013616 (2009).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep32442_CR36","doi-asserted-by":"publisher","first-page":"4371","DOI":"10.1073\/pnas.0911295107","volume":"107","author":"SB Beres","year":"2010","unstructured":"Beres, S. B. et al. Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics. Proc Natl Acad Sci USA 107, 4371\u20134376 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep32442_CR37","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1086\/430618","volume":"192","author":"NM Green","year":"2005","unstructured":"Green, N. M. et al. Genome sequence of a serotype M28 strain of group A Streptococcus: potential new insights into puerperal sepsis and bacterial disease specificity. J Infect Dis 192, 760\u2013770 (2005).","journal-title":"J Infect Dis"},{"key":"BFsrep32442_CR38","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1086\/432514","volume":"192","author":"P Sumby","year":"2005","unstructured":"Sumby, P. et al. Evolutionary origin and emergence of a highly successful clone of serotype M1 group A Streptococcus involved multiple horizontal gene transfer events. J Infect Dis 192, 771\u2013782 (2005).","journal-title":"J Infect Dis"},{"key":"BFsrep32442_CR39","doi-asserted-by":"publisher","first-page":"e1000817","DOI":"10.1371\/journal.ppat.1000817","volume":"6","author":"SA Shelburne","year":"2010","unstructured":"Shelburne, S. A. et al. A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection. PLoS Pathog 6, e1000817 (2010).","journal-title":"PLoS Pathog"},{"key":"BFsrep32442_CR40","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S1473-3099(05)70267-X","volume":"5","author":"JR Carapetis","year":"2005","unstructured":"Carapetis, J. R., Steer, A. C., Mulholland, E. K. & Weber, M. The global burden of group A streptococcal diseases. Lancet Infect Dis 5, 685\u2013694 (2005).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep32442_CR41","doi-asserted-by":"publisher","first-page":"e0129417","DOI":"10.1371\/journal.pone.0129417","volume":"10","author":"ZW Stetzner","year":"2015","unstructured":"Stetzner, Z. W. et al. Serotype M3 and M28 Group A Streptococci Have Distinct Capacities to Evade Neutrophil and TNF-alpha Responses and to Invade Soft Tissues. PLoS One 10, e0129417 (2015).","journal-title":"PLoS One"},{"key":"BFsrep32442_CR42","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/mmi.12537","volume":"92","author":"J Willenborg","year":"2014","unstructured":"Willenborg, J., de Greeff, A., Jarek, M., Valentin-Weigand, P. & Goethe, R. The CcpA regulon of Streptococcus suis reveals novel insights into the regulation of the streptococcal central carbon metabolism by binding of CcpA to two distinct binding motifs. Mol Microbiol 92, 61\u201383 (2014).","journal-title":"Mol Microbiol"},{"key":"BFsrep32442_CR43","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1186\/1471-2164-13-401","volume":"13","author":"BC Marciniak","year":"2012","unstructured":"Marciniak, B. C. et al. High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis. BMC Genomics 13, 401 (2012).","journal-title":"BMC Genomics"},{"key":"BFsrep32442_CR44","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/nrmicro2624","volume":"9","author":"EM Molloy","year":"2011","unstructured":"Molloy, E. M., Cotter, P. D., Hill, C., Mitchell, D. A. & Ross, R. P. Streptolysin S-like virulence factors: the continuing sagA. Nat Rev Microbiol 9, 670\u2013681 (2011).","journal-title":"Nat Rev Microbiol"},{"key":"BFsrep32442_CR45","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1086\/603541","volume":"200","author":"CE Turner","year":"2009","unstructured":"Turner, C. E., Kurupati, P., Jones, M. D., Edwards, R. J. & Sriskandan, S. Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes infection. J Infect Dis 200, 555\u2013563 (2009).","journal-title":"J Infect Dis"},{"key":"BFsrep32442_CR46","doi-asserted-by":"publisher","first-page":"3046","DOI":"10.1093\/emboj\/20.12.3046","volume":"20","author":"M Collin","year":"2001","unstructured":"Collin, M. & Olsen, A. EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG. EMBO J 20, 3046\u20133055 (2001).","journal-title":"EMBO J"},{"key":"BFsrep32442_CR47","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1186\/1471-2164-14-745","volume":"14","author":"PS Novichkov","year":"2013","unstructured":"Novichkov, P. S. et al. RegPrecise 3.0\u2013a resource for genome-scale exploration of transcriptional regulation in bacteria. BMC Genomics 14, 745 (2013).","journal-title":"BMC Genomics"},{"key":"BFsrep32442_CR48","doi-asserted-by":"crossref","unstructured":"Gupta, R. et al. Deletion of arcD in Streptococcus pneumoniae D39 impairs its capsule and attenuates the virulence. Infect Immun (2013).","DOI":"10.1128\/IAI.00778-13"},{"key":"BFsrep32442_CR49","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1111\/j.2041-1014.2012.00658.x","volume":"27","author":"JL Brittan","year":"2012","unstructured":"Brittan, J. L., Buckeridge, T. J., Finn, A., Kadioglu, A. & Jenkinson, H. F. Pneumococcal neuraminidase A: an essential upper airway colonization factor for Streptococcus pneumoniae. Mol Oral Microbiol 27, 270\u2013283 (2012).","journal-title":"Mol Oral Microbiol"},{"key":"BFsrep32442_CR50","doi-asserted-by":"publisher","first-page":"e1004088","DOI":"10.1371\/journal.ppat.1004088","volume":"10","author":"N Horstmann","year":"2014","unstructured":"Horstmann, N. et al. Dual-site phosphorylation of the control of virulence regulator impacts group a streptococcal global gene expression and pathogenesis. PLoS Pathog 10, e1004088 (2014).","journal-title":"PLoS Pathog"},{"key":"BFsrep32442_CR51","doi-asserted-by":"publisher","first-page":"e5","DOI":"10.1371\/journal.ppat.0020005","volume":"2","author":"P Sumby","year":"2006","unstructured":"Sumby, P., Whitney, A. R., Graviss, E. A., DeLeo, F. R. & Musser, J. M. Genome-wide analysis of group A streptococci reveals a mutation that modulates global phenotype and disease specificity. PLoS Pathog 2, e5 (2006).","journal-title":"PLoS Pathog"},{"key":"BFsrep32442_CR52","doi-asserted-by":"publisher","first-page":"4923","DOI":"10.1016\/j.vaccine.2009.06.042","volume":"27","author":"CE Turner","year":"2009","unstructured":"Turner, C. E., Kurupati, P., Wiles, S., Edwards, R. J. & Sriskandan, S. Impact of immunization against SpyCEP during invasive disease with two streptococcal species: Streptococcus pyogenes and Streptococcus equi. Vaccine 27, 4923\u20134929 (2009).","journal-title":"Vaccine"},{"key":"BFsrep32442_CR53","doi-asserted-by":"publisher","first-page":"4605","DOI":"10.1128\/IAI.00477-06","volume":"74","author":"SA Shelburne 3rd","year":"2006","unstructured":"Shelburne, S. A. 3rd et al. Maltodextrin utilization plays a key role in the ability of group A Streptococcus to colonize the oropharynx. Infect Immun 74, 4605\u20134614 (2006).","journal-title":"Infect Immun"},{"key":"BFsrep32442_CR54","doi-asserted-by":"publisher","first-page":"127","DOI":"10.4137\/EBO.S11250","volume":"9","author":"T Magoc","year":"2013","unstructured":"Magoc, T., Wood, D. & Salzberg, S. L. EDGE-pro: Estimated Degree of Gene Expression in Prokaryotic Genomes. Evol Bioinform Online 9, 127\u2013136 (2013).","journal-title":"Evol Bioinform Online"},{"key":"BFsrep32442_CR55","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","volume":"11","author":"S Anders","year":"2010","unstructured":"Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol 11, R106 (2010).","journal-title":"Genome Biol"},{"key":"BFsrep32442_CR56","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1471-2105-10-48","volume":"10","author":"E Eden","year":"2009","unstructured":"Eden, E., Navon, R., Steinfeld, I., Lipson, D. & Yakhini, Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics 10, 48 (2009).","journal-title":"BMC Bioinformatics"},{"key":"BFsrep32442_CR57","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.resmic.2014.08.004","volume":"165","author":"D Travisany","year":"2014","unstructured":"Travisany, D. et al. A new genome of Acidithiobacillus thiooxidans provides insights into adaptation to a bioleaching environment. Res Microbiol 165, 743\u2013752 (2014).","journal-title":"Res Microbiol"},{"key":"BFsrep32442_CR58","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1101\/gr.10.6.744","volume":"10","author":"AM McGuire","year":"2000","unstructured":"McGuire, A. M., Hughes, J. D. & Church, G. M. Conservation of DNA regulatory motifs and discovery of new motifs in microbial genomes. Genome Res 10, 744\u2013757 (2000).","journal-title":"Genome Res"},{"key":"BFsrep32442_CR59","doi-asserted-by":"publisher","first-page":"W369","DOI":"10.1093\/nar\/gkl198","volume":"34","author":"TL Bailey","year":"2006","unstructured":"Bailey, T. L., Williams, N., Misleh, C. & Li, W. W. MEME: discovering and analyzing DNA and protein sequence motifs. Nucleic Acids Res 34, W369\u2013W373 (2006).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep32442_CR60","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1186\/1471-2164-9-488","volume":"9","author":"T Hulsen","year":"2008","unstructured":"Hulsen, T., de Vlieg, J. & Alkema, W. BioVenn - a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. BMC Genomics 9, 488 (2008).","journal-title":"BMC Genomics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep32442","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32442.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32442.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T04:31:25Z","timestamp":1718771485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep32442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,1]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,10,17]]}},"alternative-id":["BFsrep32442"],"URL":"https:\/\/doi.org\/10.1038\/srep32442","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,1]]},"assertion":[{"value":"18 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32442"}}