{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:33:35Z","timestamp":1787960015010,"version":"build-2784847793"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"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>Group A Streptoccocus (GAS) is among the most diverse of all human pathogens, responsible for a range of clinical manifestations, from mild superficial infections such as pharyngitis to serious invasive infections such as necrotising fasciitis and sepsis. The drivers of these different disease phenotypes are not known. The GAS cholesterol-dependent cytolysin, Streptolysin O (SLO), has well established cell and tissue destructive activity. We investigated the role of SLO in determining disease outcome in vivo, by using two different clinical lineages; the recently emerged hypervirulent outbreak <jats:italic>emm<\/jats:italic> type 32.2 strains, which result in sepsis, and the <jats:italic>emm<\/jats:italic> type 1.0 strains which cause septic arthritis. Using clinically relevant in vivo mouse models of sepsis and a novel septic arthritis model, we found that the amount and activity of SLO was vital in determining the course of infection. The <jats:italic>emm<\/jats:italic> type 32.2 strain produced large quantities of highly haemolytic SLO that resulted in rapid development of sepsis. By contrast, the reduced concentration and lower haemolytic activity of <jats:italic>emm<\/jats:italic> type\u00a01.0 SLO led to translocation of bacteria from blood to joints. Importantly, sepsis associated strains that were attenuated by deletion or inhibition of SLO, then also translocated to the joint, confirming the key role of SLO in determining infection niche. Our findings demonstrate that SLO is key to in vivo phenotype and disease outcome. Careful consideration should be given to novel therapy or vaccination strategies that target SLO. Whilst neutralising SLO activity may reduce severe invasive disease, it has the potential to promote chronic inflammatory conditions such as septic arthritis.<\/jats:p>","DOI":"10.1038\/s41598-021-97866-4","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T20:06:05Z","timestamp":1632945965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Streptolysin O concentration and activity is central to in vivo phenotype and disease outcome in Group A Streptococcus infection"],"prefix":"10.1038","volume":"11","author":[{"given":"Jenny","family":"Clarke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murielle","family":"Baltazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansoor","family":"Alsahag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros","family":"Panagiotou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Pouget","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Paxton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Pollakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Everett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"French","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aras","family":"Kadioglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"issue":"11","key":"97866_CR1","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(11), 685\u2013694 (2005).","journal-title":"Lancet. Infect. Dis"},{"key":"97866_CR2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/clinids\/14.1.2","volume":"14","author":"DL Stevens","year":"1992","unstructured":"Stevens, D. L. Invasive group A streptococcus infections\u2014clinical infectious diseases\u202f: an official publication of the Infectious Diseases Society of America. Clin. Infect. Dis. 14, 2\u201313 (1992).","journal-title":"Clin. Infect. Dis."},{"issue":"2","key":"97866_CR3","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1128\/CMR.00101-13","volume":"27","author":"MJ Walker","year":"2014","unstructured":"Walker, M. J. et al. Disease manifestations and pathogenic mechanisms of group a Streptococcus. Clin. Microbiol. Rev. 27(2), 264\u2013301 (2014).","journal-title":"Clin. Microbiol. Rev."},{"issue":"3","key":"97866_CR4","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1128\/CMR.13.3.470","volume":"13","author":"MW Cunningham","year":"2000","unstructured":"Cunningham, M. W. Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 13(3), 470\u2013511 (2000).","journal-title":"Clin. Microbiol. Rev."},{"issue":"9","key":"97866_CR5","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1172\/JCI38095","volume":"119","author":"JM Musser","year":"2009","unstructured":"Musser, J. M. & Shelburne, S. A. 3rd. A decade of molecular pathogenomic analysis of group A Streptococcus. J. Clin. Investig. 119(9), 2455\u20132463 (2009).","journal-title":"J. Clin. Investig."},{"issue":"2","key":"97866_CR6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1002\/path.2274","volume":"214","author":"S Sriskandan","year":"2008","unstructured":"Sriskandan, S. & Altmann, D. M. The immunology of sepsis. J. Pathol. 214(2), 211\u2013223 (2008).","journal-title":"J. Pathol."},{"key":"97866_CR7","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1038\/nm1202-800","volume":"8","author":"M Kotb","year":"2002","unstructured":"Kotb, M. et al. An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nat. Med. 8, 1398 (2002).","journal-title":"Nat. Med."},{"issue":"4","key":"97866_CR8","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1128\/jcm.34.4.953-958.1996","volume":"34","author":"B Beall","year":"1996","unstructured":"Beall, B., Facklam, R. & Thompson, T. Sequencing emm-specific PCR products for routine and accurate typing of group A streptococci. J. Clin. Microbiol. 34(4), 953\u2013958 (1996).","journal-title":"J. Clin. Microbiol."},{"issue":"9","key":"97866_CR9","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.2165\/11634180-000000000-00000","volume":"72","author":"AC Steer","year":"2012","unstructured":"Steer, A. C., Lamagni, T., Curtis, N. & Carapetis, J. R. Invasive group a streptococcal disease: epidemiology, pathogenesis and management. Drugs 72(9), 1213\u20131227 (2012).","journal-title":"Drugs"},{"issue":"6","key":"97866_CR10","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1086\/515310","volume":"177","author":"G Molinari","year":"1998","unstructured":"Molinari, G. & Chhatwal, G. S. Invasion and survival of Streptococcus pyogenes in eukaryotic cells correlates with the source of the clinical isolates. J. Infect. Dis. 177(6), 1600\u20131607 (1998).","journal-title":"J. Infect. Dis."},{"issue":"4","key":"97866_CR11","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1006\/mpat.1999.0302","volume":"27","author":"M Shiseki","year":"1999","unstructured":"Shiseki, M. et al. Comparison of pathogenic factors expressed by group A Streptococci isolated from patients with streptococcal toxic shock syndrome and scarlet fever. Microb. Pathog. 27(4), 243\u2013252 (1999).","journal-title":"Microb. Pathog."},{"issue":"11","key":"97866_CR12","doi-asserted-by":"publisher","first-page":"6362","DOI":"10.1128\/IAI.68.11.6362-6369.2000","volume":"68","author":"RG Kansal","year":"2000","unstructured":"Kansal, R. G., McGeer, A., Low, D. E., Norrby-Teglund, A. & Kotb, M. Inverse relation between disease severity and expression of the streptococcal cysteine protease, SpeB, among clonal M1T1 isolates recovered from invasive group A streptococcal infection cases. Infect. Immun. 68(11), 6362\u20136369 (2000).","journal-title":"Infect. Immun."},{"issue":"2","key":"97866_CR13","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1099\/mic.0.26826-0","volume":"150","author":"MS Rezcallah","year":"2004","unstructured":"Rezcallah, M. S., Boyle, M. D. P. & Sledjeski, D. D. Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity. Microbiology 150(2), 365\u2013371 (2004).","journal-title":"Microbiology"},{"issue":"2","key":"97866_CR14","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1128\/IAI.68.2.744-751.2000","volume":"68","author":"R Raeder","year":"2000","unstructured":"Raeder, R., Harokopakis, E., Hollingshead, S. & Boyle, M. D. P. Absence of SpeB production in virulent large capsular forms of group A streptococcal strain 64. Infect. Immun. 68(2), 744\u2013751 (2000).","journal-title":"Infect. Immun."},{"issue":"8","key":"97866_CR15","doi-asserted-by":"publisher","first-page":"4988","DOI":"10.1128\/IAI.69.8.4988-4995.2001","volume":"69","author":"SU Kazmi","year":"2001","unstructured":"Kazmi, S. U. et al. Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group A streptococcal isolates in vivo. Infect. Immun. 69(8), 4988\u20134995 (2001).","journal-title":"Infect. Immun."},{"issue":"10","key":"97866_CR16","doi-asserted-by":"publisher","first-page":"6079","DOI":"10.1128\/IAI.71.10.6079-6082.2003","volume":"71","author":"TC Smith","year":"2003","unstructured":"Smith, T. C., Sledjeski, D. D. & Boyle, M. D. P. Streptococcus pyogenes infection in mouse skin leads to a time-dependent up-regulation of protein H expression. Infect. Immun. 71(10), 6079\u20136082 (2003).","journal-title":"Infect. Immun."},{"issue":"1","key":"97866_CR17","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(1), e5 (2006).","journal-title":"PLoS Pathog."},{"issue":"7","key":"97866_CR18","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1128\/iai.57.7.2037-2042.1989","volume":"57","author":"AM Berry","year":"1989","unstructured":"Berry, A. M., Yother, J., Briles, D. E., Hansman, D. & Paton, J. C. Reduced virulence of a defined pneumolysin-negative mutant of Streptococcus pneumoniae. Infect. Immun. 57(7), 2037\u20132042 (1989).","journal-title":"Infect. Immun."},{"issue":"6","key":"97866_CR19","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1083\/jcb.200202121","volume":"156","author":"S Dramsi","year":"2002","unstructured":"Dramsi, S., Listeriolysin, P. & Listeriolysin, O. a genuine cytolysin optimized for an intracellular parasite. J. Cell Biol. 156(6), 943\u2013946 (2002).","journal-title":"J. Cell Biol."},{"issue":"4","key":"97866_CR20","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S1438-4221(00)80039-9","volume":"290","author":"JE Alouf","year":"2000","unstructured":"Alouf, J. E. Cholesterol-binding cytolytic protein toxins. Int. J. Med. Microbiol. 290(4), 351\u2013356 (2000).","journal-title":"Int. J. Med. Microbiol."},{"issue":"1","key":"97866_CR21","doi-asserted-by":"crossref","first-page":"e00387-12","DOI":"10.1128\/mBio.00387-12","volume":"4","author":"E Chiarot","year":"2013","unstructured":"Chiarot, E. et al. Targeted amino acid substitutions impair streptolysin O toxicity and group A streptococcus virulence. mBiol. 4(1), e00387-12 (2013).","journal-title":"mBiol."},{"issue":"6","key":"97866_CR22","doi-asserted-by":"publisher","first-page":"9M111.015693","DOI":"10.1074\/mcp.M111.015693","volume":"11","author":"G Bensi","year":"2012","unstructured":"Bensi, G. et al. Multi high-throughput approach for highly selective identification of vaccine candidates: the Group A Streptococcus case. Mol Cell Proteomics MCP. 11(6), 9M111.015693 (2012).","journal-title":"Mol Cell Proteomics MCP."},{"issue":"1","key":"97866_CR23","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1128\/IAI.71.1.446-455.2003","volume":"71","author":"G Sierig","year":"2003","unstructured":"Sierig, G., Cywes, C., Wessels, M. R. & Ashbaugh, C. D. Cytotoxic effects of streptolysin O and streptolysin S enhance the virulence of poorly encapsulated group A streptococci. Infect. Immun. 71(1), 446\u2013455 (2003).","journal-title":"Infect. Immun."},{"issue":"2","key":"97866_CR24","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1074\/jbc.M804632200","volume":"284","author":"AM Timmer","year":"2009","unstructured":"Timmer, A. M. et al. Streptolysin O promotes group A streptococcus immune evasion by accelerated macrophage apoptosis. J. Biol. Chem. 284(2), 862\u2013871 (2009).","journal-title":"J. Biol. Chem."},{"issue":"5","key":"97866_CR25","doi-asserted-by":"publisher","first-page":"01378","DOI":"10.1128\/mBio.01378-15","volume":"6","author":"L Zhu","year":"2015","unstructured":"Zhu, L., Olsen, R. J., Nasser, W., de la Riva, M. I. & Musser, J. M. Trading capsule for increased cytotoxin production: contribution to virulence of a newly emerged clade of emm89 streptococcus pyogenes. MBio 6(5), 01378\u201301415 (2015).","journal-title":"MBio"},{"issue":"2","key":"97866_CR26","first-page":"181","volume":"34","author":"JG Howard","year":"1953","unstructured":"Howard, J. G. & Wallace, K. R. The comparative resistances of the red cells of various species to haemolysis by streptolysin O and by saponin. Br. J. Exp. Pathol. 34(2), 181\u2013184 (1953).","journal-title":"Br. J. Exp. Pathol."},{"issue":"3","key":"97866_CR27","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/j.1476-5381.1968.tb00445.x","volume":"32","author":"BN Halpern","year":"1968","unstructured":"Halpern, B. N. & Rahman, S. Studies on the cardiotoxicity of streptolysin O. Br. J. Pharmacol. Chemother. 32(3), 441\u2013452 (1968).","journal-title":"Br. J. Pharmacol. Chemother."},{"issue":"11","key":"97866_CR28","doi-asserted-by":"publisher","first-page":"6384","DOI":"10.1128\/IAI.68.11.6384-6390.2000","volume":"68","author":"B Limbago","year":"2000","unstructured":"Limbago, B., Penumalli, V., Weinrick, B. & Scott, J. R. Role of streptolysin O in a mouse model of invasive group A streptococcal disease. Infect. Immun. 68(11), 6384\u20136390 (2000).","journal-title":"Infect. Immun."},{"issue":"3","key":"97866_CR29","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.ajpath.2016.11.003","volume":"187","author":"L Zhu","year":"2017","unstructured":"Zhu, L. et al. Contribution of secreted NADase and streptolysin O to the pathogenesis of epidemic serotype M1 streptococcus pyogenes infections. Am. J. Pathol. 187(3), 605\u2013613 (2017).","journal-title":"Am. J. Pathol."},{"issue":"6","key":"97866_CR30","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1128\/JCM.00191-17","volume":"55","author":"JE Cornick","year":"2017","unstructured":"Cornick, J. E. et al. Epidemiological and molecular characterization of an invasive group A streptococcus emm32.2 outbreak. J. Clin. Microbiol. 55(6), 1837\u20131846 (2017).","journal-title":"J. Clin. Microbiol."},{"issue":"1","key":"97866_CR31","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nbt.3037","volume":"33","author":"BD Henry","year":"2015","unstructured":"Henry, B. D. et al. Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nat Biotechnol. 33(1), 81\u201388 (2015).","journal-title":"Nat Biotechnol."},{"issue":"5","key":"97866_CR32","doi-asserted-by":"publisher","first-page":"e1004836","DOI":"10.1371\/journal.ppat.1004836","volume":"11","author":"Y Alhamdi","year":"2015","unstructured":"Alhamdi, Y. et al. Circulating pneumolysin is a potent inducer of cardiac injury during pneumococcal infection. PLoS Pathog. 11(5), e1004836 (2015).","journal-title":"PLoS Pathog."},{"issue":"12","key":"97866_CR33","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1111\/cmi.12531","volume":"17","author":"TC Barnett","year":"2015","unstructured":"Barnett, T. C. et al. Streptococcal toxins: role in pathogenesis and disease. Cell. Microbiol. 17(12), 1721\u20131741 (2015).","journal-title":"Cell. Microbiol."},{"key":"97866_CR34","doi-asserted-by":"publisher","first-page":"581","DOI":"10.3389\/fimmu.2015.00581","volume":"6","author":"S Uchiyama","year":"2015","unstructured":"Uchiyama, S. et al. Streptolysin O rapidly impairs neutrophil oxidative burst and antibacterial responses to group A streptococcus. Front. Immunol. 6, 581 (2015).","journal-title":"Front. Immunol."},{"key":"97866_CR35","doi-asserted-by":"publisher","first-page":"518","DOI":"10.3389\/fimmu.2015.00518","volume":"6","author":"CN LaRock","year":"2015","unstructured":"LaRock, C. N. & Nizet, V. Inflammasome\/IL-1\u03b2 responses to streptococcal pathogens. Front. Immunol. 6, 518 (2015).","journal-title":"Front. Immunol."},{"issue":"9","key":"97866_CR36","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.1172\/JCI82478","volume":"125","author":"L Zhu","year":"2015","unstructured":"Zhu, L. et al. A molecular trigger for intercontinental epidemics of group A streptococcus. J. Clin. Investig. 125(9), 3545\u20133559 (2015).","journal-title":"J. Clin. Investig."},{"issue":"10","key":"97866_CR37","doi-asserted-by":"publisher","first-page":"6562","DOI":"10.1128\/IAI.73.10.6562-6566.2005","volume":"73","author":"AL Bricker","year":"2005","unstructured":"Bricker, A. L., Carey, V. J. & Wessels, M. R. Role of NADase in virulence in experimental invasive group A streptococcal infection. Infect. Immun. 73(10), 6562\u20136566 (2005).","journal-title":"Infect. Immun."},{"issue":"4","key":"97866_CR38","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1128\/CMR.15.4.527-544.2002","volume":"15","author":"ME Shirtliff","year":"2002","unstructured":"Shirtliff, M. E. & Mader, J. T. Acute septic arthritis. Clin. Microbiol. Rev. 15(4), 527\u2013544 (2002).","journal-title":"Clin. Microbiol. Rev."},{"issue":"26","key":"97866_CR39","doi-asserted-by":"publisher","first-page":"2953","DOI":"10.1016\/j.vaccine.2016.03.073","volume":"34","author":"AC Steer","year":"2016","unstructured":"Steer, A. C. et al. Status of research and development of vaccines for Streptococcus pyogenes. Vaccine. 34(26), 2953\u20132958 (2016).","journal-title":"Vaccine."},{"issue":"3","key":"97866_CR40","doi-asserted-by":"publisher","first-page":"e1002574","DOI":"10.1371\/journal.ppat.1002574","volume":"8","author":"LJ Hathaway","year":"2012","unstructured":"Hathaway, L. J. et al. Capsule type of streptococcus pneumoniae determines growth phenotype. PLoS Pathog. 8(3), e1002574 (2012).","journal-title":"PLoS Pathog."},{"issue":"1","key":"97866_CR41","doi-asserted-by":"publisher","first-page":"e8902","DOI":"10.1371\/journal.pone.0008902","volume":"5","author":"C Hyams","year":"2010","unstructured":"Hyams, C., Tam, J. C. H., Brown, J. S. & Gordon, S. B. C3b\/iC3b deposition on streptococcus pneumoniae is not affected by HIV infection. PLoS ONE 5(1), e8902 (2010).","journal-title":"PLoS ONE"},{"issue":"4","key":"97866_CR42","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1128\/cdli.4.4.415-422.1997","volume":"4","author":"S Romero-Steiner","year":"1997","unstructured":"Romero-Steiner, S. et al. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clin. Diagn. Lab. Immunol. 4(4), 415\u2013422 (1997).","journal-title":"Clin. Diagn. Lab. Immunol."},{"issue":"1","key":"97866_CR43","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1529\/biophysj.108.139154","volume":"96","author":"J Lam","year":"2009","unstructured":"Lam, J., Herant, M., Dembo, M. & Heinrich, V. Baseline mechanical characterization of J774 macrophages. Biophys. J . 96(1), 248\u2013254 (2009).","journal-title":"Biophys. J ."},{"key":"97866_CR44","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/9780470942390.mo110217","volume":"2","author":"T Burkholder","year":"2012","unstructured":"Burkholder, T., Foltz, C., Karlsson, E., Linton, C. G. & Smith, J. M. Health evaluation of experimental laboratory mice. Curr. Protocols Mouse Biol. 2, 145\u2013165 (2012).","journal-title":"Curr. Protocols Mouse Biol."},{"issue":"5","key":"97866_CR45","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(5), 771\u2013782 (2005).","journal-title":"J. Infect. Dis."},{"issue":"4","key":"97866_CR46","doi-asserted-by":"publisher","first-page":"e62433","DOI":"10.1371\/journal.pone.0062433","volume":"8","author":"L Franklin","year":"2013","unstructured":"Franklin, L. et al. The AgI\/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes. PLoS ONE 8(4), e62433 (2013).","journal-title":"PLoS ONE"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97866-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97866-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97866-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T15:59:17Z","timestamp":1670083157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-97866-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,24]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["97866"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-97866-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,24]]},"assertion":[{"value":"25 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19011"}}