{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:56:55Z","timestamp":1790114215823,"version":"4.0.1"},"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["096413\/Z\/11\/Z"],"award-info":[{"award-number":["096413\/Z\/11\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Streptococcus pneumoniae<\/jats:italic> is an important cause of fatal pneumonia in humans. These bacteria express virulence factors, such as the toxins pneumolysin and autolysin, that drive host inflammatory responses. In this study we confirm loss of pneumolysin and autolysin function in a group of clonal pneumococci that have a chromosomal deletion resulting in a pneumolysin-autolysin fusion gene \u0394(<jats:italic>lytA\u2019-ply\u2019<\/jats:italic>)593. The \u0394(<jats:italic>lytA\u2019-ply\u2019<\/jats:italic>)593 pneumococci strains naturally occur in horses and infection is associated with mild clinical signs. Here we use immortalized and primary macrophage in vitro models, which include pattern recognition receptor knock-out cells, and a murine acute pneumonia model to show that a \u0394(<jats:italic>lytA\u2019-ply\u2019<\/jats:italic>)593 strain induces cytokine production by cultured macrophages, however, unlike the serotype-matched <jats:italic>ply<\/jats:italic><jats:sup>+<\/jats:sup><jats:italic>lytA<\/jats:italic><jats:sup>+<\/jats:sup> strain, it induces less tumour necrosis factor \u03b1 (TNF\u03b1) and no interleukin-1\u03b2 production. The TNF\u03b1 induced by the \u0394(<jats:italic>lytA\u2019-ply\u2019<\/jats:italic>)593 strain requires MyD88 but, in contrast to the <jats:italic>ply<\/jats:italic><jats:sup>+<\/jats:sup><jats:italic>lytA<\/jats:italic><jats:sup>+<\/jats:sup> strain, is not reduced in cells lacking TLR2, 4 or 9. In comparison to the <jats:italic>ply<\/jats:italic><jats:sup>+<\/jats:sup><jats:italic>lytA<\/jats:italic><jats:sup>+<\/jats:sup> strain in a mouse model of acute pneumonia, infection with the \u0394(<jats:italic>lytA\u2019-ply\u2019<\/jats:italic>)593 strain resulted in less severe lung pathology, comparable levels of interleukin-1\u03b1, but minimal release of other pro-inflammatory cytokines, including interferon-\u03b3, interleukin-6 and TNF\u03b1. These results suggest a mechanism by which a naturally occurring \u0394(<jats:italic>lytA\u2019-ply\u2019<\/jats:italic>)593 mutant strain of <jats:italic>S<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> that resides in a non-human host has reduced inflammatory and invasive capacity compared to a human <jats:italic>S<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> strain. These data probably explain the relatively mild clinical disease in response to <jats:italic>S<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> infection seen in horses in comparison to humans.<\/jats:p>","DOI":"10.1371\/journal.pone.0282843","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T18:36:44Z","timestamp":1678473404000},"page":"e0282843","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Naturally-occurring serotype 3 Streptococcus pneumoniae strains that lack functional pneumolysin and autolysin have attenuated virulence but induce localized protective immune responses"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9530-7106","authenticated-orcid":true,"given":"\u0397\u03b1nnah E.","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Tourlomousis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1880-0095","authenticated-orcid":true,"given":"Gavin K.","family":"Paterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Webster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare E.","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"pone.0282843.ref001","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/S0140-6736(09)61114-4","article-title":"Pathogenesis, treatment, and prevention of pneumococcal pneumonia","volume":"374","author":"T van der Poll","year":"2009","journal-title":"Lancet"},{"key":"pone.0282843.ref002","first-page":"97","article-title":"Pneumococcal vaccines","volume":"78","author":"World Health Organisation","year":"2003","journal-title":"Weekly epidemiological record"},{"key":"pone.0282843.ref003","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1017\/S0950268805004012","article-title":"A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting","volume":"133","author":"M Hussain","year":"2005","journal-title":"Epidemiol Infect"},{"key":"pone.0282843.ref004","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1086\/431524","article-title":"Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study","volume":"192","author":"D Goldblatt","year":"2005","journal-title":"Journal of Infectious Diseases"},{"key":"pone.0282843.ref005","doi-asserted-by":"crossref","DOI":"10.1038\/s41579-018-0001-8","article-title":"Streptococcus pneumoniae: transmissoin, colonizatoin and invasion","author":"JN Weiser","year":"2018"},{"key":"pone.0282843.ref006","first-page":"5","article-title":"Pneumococcal capsular polysaccharide structure predicts serotype prevalence","author":"DM Weinberger","year":"2009","journal-title":"PLoS Pathog"},{"key":"pone.0282843.ref007","first-page":"1","article-title":"Sugar-Coated Killer: Serotype 3 Pneumococcal Disease.","volume":"10","author":"JN Luck","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0282843.ref008","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1086\/505710","article-title":"Capsular serotype-specific attack rates and duration of carriage of Streptococcus pneumoniae in a population of children","volume":"194","author":"KL Sleeman","year":"2006","journal-title":"Journal of Infectious Diseases"},{"key":"pone.0282843.ref009","first-page":"10","article-title":"The genomics of Streptococcus Pneumoniae carriage isolates from UK children and their household contacts, Pre-PCV7 to Post-PCV13","author":"CL Sheppard","year":"2019","journal-title":"Genes (Basel)."},{"key":"pone.0282843.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12879-015-1147-x","article-title":"Pneumococcal serotype evolution in Western Europe.","volume":"15","author":"M Tin Tin Htar","year":"2015","journal-title":"BMC Infect Dis"},{"key":"pone.0282843.ref011","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.3201\/eid1907.121830","article-title":"Pneumococcal serotypes before and after introduction of conjugate vaccines, United States, 1999\u20132011","volume":"19","author":"SS Richter","year":"2013","journal-title":"Emerg Infect Dis"},{"key":"pone.0282843.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.ppat.1007438","article-title":"Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci.","volume":"14","author":"T Azarian","year":"2018","journal-title":"PLoS Pathog"},{"key":"pone.0282843.ref013","first-page":"10","article-title":"Evolution of streptococcus pneumoniae serotype 3 in England and Wales: A major vaccine evader","author":"N Groves","year":"2019","journal-title":"Genes (Basel)."},{"key":"pone.0282843.ref014","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1086\/655828","article-title":"Risk of death from pneumococcal pneumonia is a stable serotype-associated property: a meta-analysis","volume":"51","author":"DM Weinberger","year":"2010","journal-title":"Clin Infect Dis"},{"key":"pone.0282843.ref015","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.2042-3306.1986.tb03591.x","article-title":"Isolation of Streptococcus pneumoniae from the respiratory tract of horses","volume":"18","author":"MH Burrell","year":"1986","journal-title":"Equine Vet J"},{"key":"pone.0282843.ref016","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1128\/JCM.43.1.120-126.2005","article-title":"Association between respiratory disease and bacterial and viral infections in British racehorses","volume":"43","author":"J Wood","year":"2005","journal-title":"J Clin Microbiol"},{"key":"pone.0282843.ref017","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1128\/IAI.67.6.2776-2782.1999","article-title":"Molecular characterization of equine isolates of Streptococcus pneumoniae: natural disruption of genes encoding the virulence factors pneumolysin and autolysin","volume":"67","author":"AM Whatmore","year":"1999","journal-title":"Infect Immun"},{"key":"pone.0282843.ref018","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1128\/jcm.20.6.1028-1030.1984","article-title":"Isolation of Streptococcus pneumoniae type 3 from equine species","volume":"20","author":"CE Benson","year":"1984","journal-title":"J Clin Microbiol"},{"key":"pone.0282843.ref019","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.2042-3306.1993.tb02970.x","article-title":"Streptococci and Pasteurella spp. associated with disease of the equine lower respiratory tract","volume":"25","author":"JLN Wood","year":"1993","journal-title":"Equine Vet J"},{"key":"pone.0282843.ref020","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.2042-3306.1994.tb04325.x","article-title":"Susceptibility of ponies to infection with Streptococcus pneumoniae (capsular type 3).","volume":"26","author":"AS Blunden","year":"1994","journal-title":"Equine Vet J"},{"key":"pone.0282843.ref021","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.2042-3306.1992.tb02866.x","article-title":"Bacteraemia and pneumonia in a neonatal foal caused by Streptococcus pneumoniae type 3","volume":"24","author":"JC Meyer","year":"1992","journal-title":"Equine Vet J"},{"key":"pone.0282843.ref022","article-title":"Cytokine Kinetics and Other Host Factors in Response to Pneumococcal Pulmonary Infection in Mice Cytokine Kinetics and Other Host Factors in Response to Pneumococcal Pulmonary Infection in Mice","author":"Y Bergeron","year":"1998","journal-title":"Infect Immun"},{"key":"pone.0282843.ref023","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.1128\/IAI.00431-10","article-title":"Inhibition of T cells provides protection against early invasive pneumococcal disease","volume":"78","author":"K LeMessurier","year":"2010","journal-title":"Infect Immun"},{"key":"pone.0282843.ref024","doi-asserted-by":"crossref","first-page":"430","DOI":"10.2119\/molmed.2014.00263","article-title":"Modular transcriptional networks of the host pulmonary response during early and late pneumococcal pneumonia","volume":"21","author":"BP Scicluna","year":"2015","journal-title":"Molecular Medicine"},{"key":"pone.0282843.ref025","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1128\/iai.65.1.257-260.1997","article-title":"Role of tumor necrosis factor alpha in pathogenesis of pneumococcal pneumonia in mice","volume":"65","author":"K Takashima","year":"1997","journal-title":"Infect Immun"},{"key":"pone.0282843.ref026","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1073\/pnas.0435928100","article-title":"Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection","volume":"100","author":"R Malley","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0282843.ref027","doi-asserted-by":"crossref","first-page":"7718","DOI":"10.1128\/IAI.73.11.7718-7726.2005","article-title":"Host and Bacterial Factors Contributing to the Clearance of Colonization by Streptococcus pneumoniae in a Murine Model","volume":"73","author":"AMC Van Rossum","year":"2005","journal-title":"Infect Immun"},{"key":"pone.0282843.ref028","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1093\/intimm\/dxn071","article-title":"Contribution of IL-1 to resistance to Streptococcus pneumoniae infection","volume":"20","author":"D Kafka","year":"2008","journal-title":"Int Immunol"},{"key":"pone.0282843.ref029","doi-asserted-by":"crossref","first-page":"e1001191","DOI":"10.1371\/journal.ppat.1001191","article-title":"Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4","volume":"6","author":"EA McNeela","year":"2010","journal-title":"PLoS Pathog"},{"key":"pone.0282843.ref030","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.4049\/jimmunol.1100381","article-title":"Critical roles of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection","volume":"187","author":"R Fang","year":"2011","journal-title":"J Immunol"},{"key":"pone.0282843.ref031","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1164\/rccm.201604-0797ED","article-title":"Toward the molecular signature of acute respiratory distress syndrome","volume":"194","author":"LK Reiss","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0282843.ref032","doi-asserted-by":"crossref","first-page":"L217","DOI":"10.1152\/ajplung.00311.2013","article-title":"The mercurial nature of neutrophils: still an enigma in ARDS","volume":"306","author":"AE Williams","year":"2014","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"pone.0282843.ref033","doi-asserted-by":"crossref","first-page":"8186","DOI":"10.1128\/JB.00690-07","article-title":"Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: Insights into the pneumococcal supragenome","volume":"189","author":"NL Hiller","year":"2007","journal-title":"J Bacteriol"},{"key":"pone.0282843.ref034","first-page":"8","article-title":"A high-resolution view of genome-wide pneumococcal transformation","author":"NJ Croucher","year":"2012","journal-title":"PLoS Pathog"},{"key":"pone.0282843.ref035","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1084\/jem.97.5.591","article-title":"Synthesis of type III pneumococcal polysaccharide by suspensions of resting cells","volume":"97","author":"AW Bernheimer","year":"1953","journal-title":"J Exp Med"},{"key":"pone.0282843.ref036","doi-asserted-by":"crossref","first-page":"R107","DOI":"10.1186\/gb-2010-11-10-r107","article-title":"Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species","volume":"11","author":"C Donati","year":"2010","journal-title":"Genome Biol"},{"key":"pone.0282843.ref037","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1128\/genomeA.00697-15","article-title":"Draft genome sequence of the Streptococcus pneumoniae Avery strain A66","volume":"3","author":"C Hahn","year":"2015","journal-title":"Genome Announc"},{"key":"pone.0282843.ref038","doi-asserted-by":"crossref","first-page":"5380","DOI":"10.4049\/jimmunol.171.10.5380","article-title":"Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection","volume":"171","author":"DH Dockrell","year":"2003","journal-title":"Journal of immunology"},{"key":"pone.0282843.ref039","doi-asserted-by":"crossref","first-page":"e742184","DOI":"10.1155\/2013\/742184","article-title":"Low pH Environmental Stress Inhibits LPS and LTA-Stimulated Proinflammatory Cytokine Production in Rat Alveolar Macrophages","volume":"2013","author":"SF Fernandez","year":"2013","journal-title":"Biomedical research international"},{"key":"pone.0282843.ref040","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1096\/fj.13-247460","article-title":"A new protective role for S100A9 in regulation of neutrophil recruitment during invasive pneumococcal pneumonia","volume":"28","author":"K De Filippo","year":"2014","journal-title":"FASEB J"},{"key":"pone.0282843.ref041","doi-asserted-by":"crossref","first-page":"4405","DOI":"10.1128\/IAI.71.8.4405-4413.2003","article-title":"Contribution of a Response Regulator to the Virulence of Streptococcus pneumoniae Is Strain Dependent","volume":"71","author":"CE Blue","year":"2003","journal-title":"Infect Immun"},{"key":"pone.0282843.ref042","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1128\/JB.01092-06","article-title":"Identification of a secreted cholesterol-dependent cytolysin (mitilysin) from Streptococcus mitis","volume":"189","author":"J Jefferies","year":"2007","journal-title":"J Bacteriol"},{"key":"pone.0282843.ref043","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1128\/iai.55.5.1184-1189.1987","article-title":"Molecular cloning, characterization, and complete nucleotide sequence of the gene for pneumolysin, the sulfhydryl-activated toxin of Streptococcus pneumoniae","volume":"55","author":"JA Walker","year":"1987","journal-title":"Infect Immun"},{"key":"pone.0282843.ref044","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1128\/IAI.74.1.586-593.2006","article-title":"Construction and immumological characterization of a novel nontoxic protective pneumolysin mutant for use in future pneumococcal vaccines","volume":"74","author":"LAS Kirkham","year":"2006","journal-title":"Infect Immun"},{"key":"pone.0282843.ref045","doi-asserted-by":"crossref","first-page":"25742","DOI":"10.1074\/jbc.M109.014886","article-title":"A TIR domain variant of MyD88 adapter-like (Mal)\/TIRAP results in loss of MyD88 binding and reduced TLR2\/TLR4 signaling","volume":"284","author":"K Nagpal","year":"2009","journal-title":"J Biol Chem"},{"key":"pone.0282843.ref046","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms12874","article-title":"CARD9 negatively regulates NLRP3-induced IL-1\u03b2 production on Salmonella infection of macrophages","volume":"7","author":"M Pereira","year":"2016","journal-title":"Nat Commun"},{"key":"pone.0282843.ref047","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1128\/IAI.68.2.492-501.2000","article-title":"Host cellular immune response to pneumococcal lung infection in mice","volume":"68","author":"A Kadioglu","year":"2000","journal-title":"Infect Immun"},{"key":"pone.0282843.ref048","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.4049\/jimmunol.172.5.3132","article-title":"Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense","volume":"172","author":"S Knapp","year":"2004","journal-title":"The Journal of Immunology"},{"key":"pone.0282843.ref049","first-page":"237","article-title":"Toll-like receptor 2 contributes to antibacterial defence against pneumolysin-deficient pneumococci","volume":"10","author":"MC Dessing","year":"2008","journal-title":"Cell Microbiol"},{"key":"pone.0282843.ref050","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2052-0492-1-2","article-title":"Evaluation of semi-quantitative scoring of Gram staining or semi-quantitative culture for the diagnosis of ventilator-associated pneumonia: A retrospective comparison with quantitative culture","volume":"1","author":"S Hashimoto","year":"2013","journal-title":"J Intensive Care."},{"key":"pone.0282843.ref051","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bj.2017.10.002","article-title":"Gasdermin: A new player to the inflammasome game.","volume":"40","author":"ES Ramos-Junior","year":"2017","journal-title":"Biomed J"},{"key":"pone.0282843.ref052","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1128\/IAI.70.3.1547-1557.2002","article-title":"Role of inflammatory mediators in resistance and susceptibility to pneumococcal infection","volume":"70","author":"AR Kerr","year":"2002","journal-title":"Infect Immun"},{"key":"pone.0282843.ref053","doi-asserted-by":"crossref","first-page":"434","DOI":"10.4049\/jimmunol.1003143","article-title":"The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia","volume":"187","author":"M Witzenrath","year":"2011","journal-title":"J Immunol"},{"key":"pone.0282843.ref054","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1165\/rcmb.2013-0015OC","article-title":"NLRP3 and ASC differentially affect the lung transcriptome during pneumococcal pneumonia","volume":"50","author":"MH Van Lieshout","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"pone.0282843.ref055","doi-asserted-by":"crossref","first-page":"e01710","DOI":"10.1128\/mBio.01710-14","article-title":"Pneumolysin activates macrophage lysosomal membrane permeabilization and executes apoptosis by distinct mechanisms without membrane pore formation","volume":"5","author":"MA Bewley","year":"2014","journal-title":"mBio"},{"key":"pone.0282843.ref056","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/nm1603","article-title":"Identification of a key pathway required for the sterile inflammatory response triggered by dying cells","volume":"13","author":"CJ Chen","year":"2007","journal-title":"Nat Med"},{"key":"pone.0282843.ref057","first-page":"064748","article-title":"Eigenbrod et al. - 2008\u2014Cutting edge critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1alpha released from dying cells.pdf","author":"T Eigenbrod","year":"2008"},{"key":"pone.0282843.ref058","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1086\/520091","article-title":"Presence of nonhemolytic pneumolysin in serotypes of Streptococcus pneumoniae associated with disease outbreaks","volume":"196","author":"JMC Jefferies","year":"2007","journal-title":"Journal of Infectious Diseases"},{"key":"pone.0282843.ref059","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1086\/499242","article-title":"Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen","volume":"42","author":"K Sj\u00f6str\u00f6m","year":"2006","journal-title":"Clinical Infectious Diseases"},{"key":"pone.0282843.ref060","first-page":"215","article-title":"Inflammasomes in pneumococcal infection: Innate immune sensing and bacterial evasion strategies","volume":"397","author":"A Rabes","year":"2016","journal-title":"Curr Top Microbiol Immunol"},{"key":"pone.0282843.ref061","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1084\/jem.181.3.973","article-title":"Characterization of the Cassette Containing Genes fo Type 3 Capsular Polysaccharide Biosynthesis in Streptococcus pneumoniae","volume":"181","author":"JP Dillard","year":"2015","journal-title":"Journal of Experimental Medicine"},{"key":"pone.0282843.ref062","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.micro.62.081307.162944","article-title":"Capsules of streptococcus pneumoniae and other bacteria: Paradigms for polysaccharide biosynthesis and regulation","volume":"65","author":"J. Yother","year":"2011","journal-title":"Annu Rev Microbiol"},{"key":"pone.0282843.ref063","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1074\/jbc.275.6.3907","article-title":"Mechanism of type 3 capsular polysaccharide synthesis in Streptococcus pneumoniae","volume":"275","author":"RT Cartee","year":"2000","journal-title":"Journal of Biological Chemistry"},{"key":"pone.0282843.ref064","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/j.1365-2958.2006.05259.x","article-title":"Control of capsular polysaccharide chain length by UDP-sugar substrate concentrations in Streptococcus pneumoniae","volume":"61","author":"CL Ventura","year":"2006","journal-title":"Mol Microbiol"},{"key":"pone.0282843.ref065","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s002849900088","article-title":"The lytA gene and the DNA region located downstream of this gene are not involved in the formation of the type 3 capsular polysaccharide of Streptococcus pneumoniae","volume":"33","author":"E Garc\u00eda","year":"1996","journal-title":"Curr Microbiol"},{"key":"pone.0282843.ref066","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1128\/IAI.73.8.4653-4667.2005","article-title":"Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells","volume":"73","author":"S Hammerschmidt","year":"2005","journal-title":"Infect Immun"},{"key":"pone.0282843.ref067","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms10859","article-title":"Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium.","volume":"7","author":"CC Kietzman","year":"2016","journal-title":"Nat Commun"},{"key":"pone.0282843.ref068","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0118181","article-title":"The polysaccharide capsule of streptococcus pneumonia partially impedes myd88- Mediated immunity during pneumonia in mice","volume":"10","author":"AF De Vos","year":"2015","journal-title":"PLoS One"},{"key":"pone.0282843.ref069","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1111\/j.1462-5822.2008.01189.x","article-title":"The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls","volume":"10","author":"LO Moreira","year":"2008","journal-title":"Cell Microbiol"},{"key":"pone.0282843.ref070","first-page":"691","article-title":"Pyogenic bacterial infections in humans with MyD88 deficiency","volume":"321","author":"H Von Bernuth","year":"2008","journal-title":"Science (1979)."},{"key":"pone.0282843.ref071","doi-asserted-by":"crossref","first-page":"4392","DOI":"10.1128\/iai.61.10.4392-4397.1993","article-title":"Identification of hydrogen peroxide as a Streptococcus pneumoniae toxin for rat alveolar epithelial cells","volume":"61","author":"PG Duane","year":"1993","journal-title":"Infect Immun"},{"key":"pone.0282843.ref072","doi-asserted-by":"crossref","first-page":"4940","DOI":"10.1128\/IAI.72.9.4940-4947.2004","article-title":"Streptococcus pneumoniae- Induced Caspase 6-Dependent Apoptosis in Lung Epithelium","volume":"72","author":"B Schmeck","year":"2004","journal-title":"Infect Immun"},{"key":"pone.0282843.ref073","first-page":"1","article-title":"Streptococcus pneumoniae-Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol.","author":"J Zahlten","year":"2014","journal-title":"Journal of Infectious Diseases"},{"key":"pone.0282843.ref074","first-page":"201424144","article-title":"Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells","author":"P Rai","year":"2015","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pone.0282843.ref075","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/nar\/gkn201","article-title":"NCBI BLAST: a better web interface","volume":"36","author":"M Johnson","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"pone.0282843.ref076","first-page":"4","article-title":"Molecular characterization of pneumococcal isolates from pets and laboratory animals","author":"M van der Linden","year":"2009","journal-title":"PLoS One"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282843","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T18:37:58Z","timestamp":1678473478000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0282843"}},"subtitle":[],"editor":[{"given":"Luis Felipe","family":"Reyes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":76,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0282843","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]}}}