{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:24:11Z","timestamp":1790663051564,"version":"4.1.0"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"2-3","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Rochester Regional Health Kidd Grant"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Microbiol Immunol"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1007\/s00430-021-00701-w","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T06:02:31Z","timestamp":1616392951000},"page":"111-120","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparison of specific in-vitro virulence gene expression and innate host response in locally invasive vs colonizer strains of Streptococcus pneumoniae"],"prefix":"10.1007","volume":"210","author":[{"given":"Naoko","family":"Fuji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Pichichero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6539-5339","authenticated-orcid":false,"given":"Ravinder","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"701_CR1","first-page":"9990","volume":"46","author":"R Aprianto","year":"2018","unstructured":"Aprianto R, Slager J, Holsappel S, Veening JW (2018) High-resolution analysis of the pneumococcal transcriptome under a wide range of infection-relevant conditions. Nucleic Acids Res 46:9990\u201310006","journal-title":"Nucleic Acids Res"},{"key":"701_CR2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.smim.2007.10.009","volume":"19","author":"SJ Aujla","year":"2007","unstructured":"Aujla SJ, Dubin PJ, Kolls JK (2007) Th17 cells and mucosal host defense. Semin Immunol 19:377\u2013382","journal-title":"Semin Immunol"},{"key":"701_CR3","doi-asserted-by":"crossref","first-page":"e00745","DOI":"10.1128\/mBio.00745-13","volume":"4","author":"K Blanchette-Cain","year":"2013","unstructured":"Blanchette-Cain K, Hinojosa CA, Akula Suresh Babu R, Lizcano A, Gonzalez-Juarbe N, Munoz-Almagro C, Sanchez CJ, Bergman MA, Orihuela CJ (2013) Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization. mBio 4:e00745-e813","journal-title":"mBio"},{"key":"701_CR4","volume-title":"Streptococcal infections","author":"G Bm","year":"2000","unstructured":"Bm G (2000) Streptococcus pneumoniae infections. In: Stevens DI KE (ed) Streptococcal infections. Oxford University Press, New York"},{"key":"701_CR5","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/INF.0b013e31828d9acc","volume":"32","author":"JR Casey","year":"2013","unstructured":"Casey JR, Kaur R, Friedel VC, Pichichero ME (2013) Acute otitis media otopathogens during 2008 to 2010 in Rochester, New York. Pediatr Infect Dis J 32:805\u2013809","journal-title":"Pediatr Infect Dis J"},{"key":"701_CR6","volume-title":"Pneumococcal Carriage The Pneumococcus","author":"DW Crook","year":"2004","unstructured":"Crook DW, Brueggemann AB, Sleeman KL, Peto TE (2004) Pneumococcal Carriage The Pneumococcus. ASM Press, Washington, DC"},{"key":"701_CR7","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1093\/cid\/cit428","volume":"57","author":"R Dagan","year":"2013","unstructured":"Dagan R, Patterson S, Juergens C, Greenberg D, Givon-Lavi N, Porat N, Gurtman A, Gruber WC, Scott DA (2013) Comparative immunogenicity and efficacy of 13-valent and 7-valent pneumococcal conjugate vaccines in reducing nasopharyngeal colonization: a randomized double-blind trial. Clin Infect Dis 57:952\u2013962","journal-title":"Clin Infect Dis"},{"key":"701_CR8","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1111\/j.1365-2958.2003.03892.x","volume":"51","author":"A Dagkessamanskaia","year":"2004","unstructured":"Dagkessamanskaia A, Moscoso M, Henard V, Guiral S, Overweg K, Reuter M, Martin B, Wells J, Claverys JP (2004) Interconnection of competence, stress and CiaR regulons in Streptococcus pneumoniae: competence triggers stationary phase autolysis of ciaR mutant cells. Mol Microbiol 51:1071\u20131086","journal-title":"Mol Microbiol"},{"key":"701_CR9","doi-asserted-by":"crossref","first-page":"e00280","DOI":"10.1128\/AEM.00280-20","volume":"86","author":"M Domenech","year":"2020","unstructured":"Domenech M, Garcia E (2020) The N-Acetylglucosaminidase LytB of Streptococcus pneumoniae Is Involved in the Structure and Formation of Biofilms. Appl Environ Microbiol 86:e00280-e320","journal-title":"Appl Environ Microbiol"},{"key":"701_CR10","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1099\/mic.0.026328-0","volume":"155","author":"V Eldholm","year":"2009","unstructured":"Eldholm V, Johnsborg O, Haugen K, Ohnstad HS, Havarstein LS (2009) Fratricide in Streptococcus pneumoniae: contributions and role of the cell wall hydrolases CbpD, LytA and LytC. Microbiology 155:2223\u20132234","journal-title":"Microbiology"},{"key":"701_CR11","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1086\/516477","volume":"175","author":"H Faden","year":"1997","unstructured":"Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y (1997) Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda\/Williamsville Pediatrics. J Infect Dis 175:1440\u20131445","journal-title":"J Infect Dis"},{"key":"701_CR12","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1046\/j.1365-2958.1999.01238.x","volume":"31","author":"P Garcia","year":"1999","unstructured":"Garcia P, Gonzalez MP, Garcia E, Lopez R, Garcia JL (1999) LytB, a novel pneumococcal murein hydrolase essential for cell separation. Mol Microbiol 31:1275\u20131281","journal-title":"Mol Microbiol"},{"key":"701_CR13","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1128\/CMR.00024-15","volume":"28","author":"KA Geno","year":"2015","unstructured":"Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP, Jones C, Konradsen HB, Nahm MH (2015) Pneumococcal capsules and their types: past, present, and future. Clin Microbiol Rev 28:871\u2013899","journal-title":"Clin Microbiol Rev"},{"key":"701_CR14","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1128\/IAI.01126-07","volume":"76","author":"DT Glover","year":"2008","unstructured":"Glover DT, Hollingshead SK, Briles DE (2008) Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis. Infect Immun 76:2767\u20132776","journal-title":"Infect Immun"},{"key":"701_CR15","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1128\/IAI.00378-10","volume":"79","author":"F Godfroid","year":"2011","unstructured":"Godfroid F, Hermand P, Verlant V, Denoel P, Poolman JT (2011) Preclinical evaluation of the Pht proteins as potential cross-protective pneumococcal vaccine antigens. Infect Immun 79:238\u2013245","journal-title":"Infect Immun"},{"key":"701_CR16","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1365-2958.1994.tb01038.x","volume":"12","author":"E Guenzi","year":"1994","unstructured":"Guenzi E, Gasc AM, Sicard MA, Hakenbeck R (1994) A two-component signal-transducing system is involved in competence and penicillin susceptibility in laboratory mutants of Streptococcus pneumoniae. Mol Microbiol 12:505\u2013515","journal-title":"Mol Microbiol"},{"key":"701_CR17","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1046\/j.1365-2958.1997.5391899.x","volume":"25","author":"S Hammerschmidt","year":"1997","unstructured":"Hammerschmidt S, Talay SR, Brandtzaeg P, Chhatwal GS (1997) SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol Microbiol 25:1113\u20131124","journal-title":"Mol Microbiol"},{"key":"701_CR18","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1046\/j.1365-2958.2000.01897.x","volume":"36","author":"S Hammerschmidt","year":"2000","unstructured":"Hammerschmidt S, Tillig MP, Wolff S, Vaerman JP, Chhatwal GS (2000) Species-specific binding of human secretory component to SpsA protein of Streptococcus pneumoniae via a hexapeptide motif. Mol Microbiol 36:726\u2013736","journal-title":"Mol Microbiol"},{"key":"701_CR19","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1128\/IAI.73.8.4653-4667.2005","volume":"73","author":"S Hammerschmidt","year":"2005","unstructured":"Hammerschmidt S, Wolff S, Hocke A, Rosseau S, Muller E, Rohde M (2005) Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun 73:4653\u20134667","journal-title":"Infect Immun"},{"key":"701_CR20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2217\/17460913.3.1.23","volume":"3","author":"WP Hanage","year":"2008","unstructured":"Hanage WP (2008) Serotype-specific problems associated with pneumococcal conjugate vaccination. Future Microbiol 3:23\u201330","journal-title":"Future Microbiol"},{"key":"701_CR21","doi-asserted-by":"crossref","first-page":"11140","DOI":"10.1073\/pnas.92.24.11140","volume":"92","author":"LS Havarstein","year":"1995","unstructured":"Havarstein LS, Coomaraswamy G, Morrison DA (1995) An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proc Natl Acad Sci USA 92:11140\u201311144","journal-title":"Proc Natl Acad Sci USA"},{"key":"701_CR22","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1016\/j.vaccine.2005.08.100","volume":"23","author":"TW Hennessy","year":"2005","unstructured":"Hennessy TW, Singleton RJ, Bulkow LR, Bruden DL, Hurlburt DA, Parks D, Moore M, Parkinson AJ, Schuchat A, Butler JC (2005) Impact of heptavalent pneumococcal conjugate vaccine on invasive disease, antimicrobial resistance and colonization in Alaska Natives: progress towards elimination of a health disparity. Vaccine 23:5464\u20135473","journal-title":"Vaccine"},{"key":"701_CR23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/1348-0421.12471","volume":"61","author":"E Hoe","year":"2017","unstructured":"Hoe E, Anderson J, Nathanielsz J, Toh ZQ, Marimla R, Balloch A, Licciardi PV (2017) The contrasting roles of Th17 immunity in human health and disease. Microbiol Immunol 61:49\u201356","journal-title":"Microbiol Immunol"},{"key":"701_CR24","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1128\/JB.173.1.372-381.1991","volume":"173","author":"FM Hui","year":"1991","unstructured":"Hui FM, Morrison DA (1991) Genetic transformation in Streptococcus pneumoniae: nucleotide sequence analysis shows comA, a gene required for competence induction, to be a member of the bacterial ATP-dependent transport protein family. J Bacteriol 173:372\u2013381","journal-title":"J Bacteriol"},{"key":"701_CR25","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1128\/IAI.00881-09","volume":"78","author":"C Hyams","year":"2010","unstructured":"Hyams C, Camberlein E, Cohen JM, Bax K, Brown JS (2010) The Streptococcus pneumoniae capsule inhibits complement activity and neutrophil phagocytosis by multiple mechanisms. Infect Immun 78:704\u2013715","journal-title":"Infect Immun"},{"key":"701_CR26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.femsle.2005.09.008","volume":"252","author":"F Iannelli","year":"2005","unstructured":"Iannelli F, Oggioni MR, Pozzi G (2005) Sensor domain of histidine kinase ComD confers competence pherotype specificity in Streptoccoccus pneumoniae. FEMS Microbiol Lett 252:321\u2013326","journal-title":"FEMS Microbiol Lett"},{"key":"701_CR27","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.1128\/JB.186.16.5258-5266.2004","volume":"186","author":"YM Ibrahim","year":"2004","unstructured":"Ibrahim YM, Kerr AR, Mccluskey J, Mitchell TJ (2004) Control of virulence by the two-component system CiaR\/H is mediated via HtrA, a major virulence factor of Streptococcus pneumoniae. J Bacteriol 186:5258\u20135266","journal-title":"J Bacteriol"},{"key":"701_CR28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1365-2958.2010.07189.x","volume":"77","author":"I Jensch","year":"2010","unstructured":"Jensch I, Gamez G, Rothe M, Ebert S, Fulde M, Somplatzki D, Bergmann S, Petruschka L, Rohde M, Nau R, Hammerschmidt S (2010) PavB is a surface-exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections. Mol Microbiol 77:22\u201343","journal-title":"Mol Microbiol"},{"key":"701_CR29","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1097\/INF.0000000000001206","volume":"35","author":"R Kaur","year":"2016","unstructured":"Kaur R, Casey JR, Pichichero ME (2016) Emerging Streptococcus pneumoniae strains colonizing the Nasopharynx in Children After 13-valent pneumococcal conjugate vaccination in comparison to the 7-valent Era, 2006\u20132015. Pediatr Infect Dis J 35:901\u2013906","journal-title":"Pediatr Infect Dis J"},{"key":"701_CR30","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa157","author":"R Kaur","year":"2020","unstructured":"Kaur R, Pham M, Yu KOA, Pichichero ME (2020) Rising pneumococcal antibiotic resistance in the post 13-valent pneumococcal conjugate vaccine era in pediatric isolates from a primary care setting. Clin Infect. https:\/\/doi.org\/10.1093\/cid\/ciaa157","journal-title":"Clin Infect"},{"key":"701_CR31","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1128\/IAI.02124-14","volume":"82","author":"R Kaur","year":"2014","unstructured":"Kaur R, Surendran N, Ochs M, Pichichero ME (2014) Human antibodies to PhtD, PcpA, and Ply reduce adherence to human lung epithelial cells and murine nasopharyngeal colonization by Streptococcus pneumoniae. Infect Immun 82:5069\u20135075","journal-title":"Infect Immun"},{"key":"701_CR32","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1097\/INF.0000000000001206","volume":"35","author":"RCJ Kaur","year":"2016","unstructured":"Kaur RCJ, Pichichero M (2016) Emerging Streptococcus pneumoniae strains colonizing the Nasopharynx in children after 13-valent (PCV13) pneumococcal conjugate vaccination in comparison to the 7-valent (PCV7) Era, 2006\u20132015. Pediatric Infect Dis J. 35:901","journal-title":"Pediatric Infect Dis J."},{"key":"701_CR33","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1016\/j.vaccine.2012.02.023","volume":"30","author":"MN Khan","year":"2012","unstructured":"Khan MN, Pichichero ME (2012) Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans. Vaccine 30:2900\u20132907","journal-title":"Vaccine"},{"key":"701_CR34","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.micinf.2012.06.007","volume":"14","author":"MN Khan","year":"2012","unstructured":"Khan MN, Sharma SK, Filkins LM, Pichichero ME (2012) PcpA of Streptococcus pneumoniae mediates adherence to nasopharyngeal and lung epithelial cells and elicits functional antibodies in humans. Microbes Infect 14:1102\u20131110","journal-title":"Microbes Infect"},{"key":"701_CR35","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cyto.2013.05.013","volume":"64","author":"BJ Kim","year":"2013","unstructured":"Kim BJ, Lee S, Berg RE, Simecka JW, Jones HP (2013) Interleukin-23 (IL-23) deficiency disrupts Th17 and Th1-related defenses against Streptococcus pneumoniae infection. Cytokine 64:375\u2013381","journal-title":"Cytokine"},{"key":"701_CR36","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S1473-3099(02)00450-4","volume":"2","author":"U Koedel","year":"2002","unstructured":"Koedel U, Scheld WM, Pfister HW (2002) Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis 2:721\u2013736","journal-title":"Lancet Infect Dis"},{"key":"701_CR37","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1128\/IAI.01696-07","volume":"76","author":"JE Kowalko","year":"2008","unstructured":"Kowalko JE, Sebert ME (2008) The Streptococcus pneumoniae competence regulatory system influences respiratory tract colonization. Infect Immun 76:3131\u20133140","journal-title":"Infect Immun"},{"key":"701_CR38","doi-asserted-by":"crossref","first-page":"e20170001","DOI":"10.1542\/peds.2017-0001","volume":"140","author":"GM Lee","year":"2017","unstructured":"Lee GM, Kleinman K, Pelton S, Lipsitch M, Huang SS, Lakoma M, Dutta-Linn M, Rett M, Hanage WP, Finkelstein JA (2017) Immunization, antibiotic use, and pneumococcal colonization over a 15-year period. Pediatrics 140:e20170001","journal-title":"Pediatrics"},{"key":"701_CR39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/mdr.1997.3.199","volume":"3","author":"R Lopez","year":"1997","unstructured":"Lopez R, Garcia E, Garcia P, Garcia JL (1997) The pneumococcal cell wall degrading enzymes: a modular design to create new lysins? Microb Drug Resist 3:199\u2013211","journal-title":"Microb Drug Resist"},{"key":"701_CR40","doi-asserted-by":"crossref","first-page":"7138","DOI":"10.4049\/jimmunol.181.10.7138","volume":"181","author":"L Lu","year":"2008","unstructured":"Lu L, Ma Z, Jokiranta TS, Whitney AR, Deleo FR, Zhang JR (2008) Species-specific interaction of Streptococcus pneumoniae with human complement factor H. J Immunol 181:7138\u20137146","journal-title":"J Immunol"},{"key":"701_CR41","doi-asserted-by":"crossref","first-page":"e1000159","DOI":"10.1371\/journal.ppat.1000159","volume":"4","author":"YJ Lu","year":"2008","unstructured":"Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kolls JK, Srivastava A, Lundgren A, Forte S, Thompson CM, Harney KF, Anderson PW, Lipsitch M, Malley R (2008) Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog 4:e1000159","journal-title":"PLoS Pathog"},{"key":"701_CR42","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1128\/IAI.00488-12","volume":"80","author":"LR Marks","year":"2012","unstructured":"Marks LR, Parameswaran GI, Hakansson AP (2012) Pneumococcal interactions with epithelial cells are crucial for optimal biofilm formation and colonization in vitro and in vivo. Infect Immun 80:2744\u20132760","journal-title":"Infect Immun"},{"key":"701_CR43","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1111\/j.1365-2958.2010.07071.x","volume":"75","author":"B Martin","year":"2010","unstructured":"Martin B, Granadel C, Campo N, Henard V, Prudhomme M, Claverys JP (2010) Expression and maintenance of ComD-ComE, the two-component signal-transduction system that controls competence of Streptococcus pneumoniae. Mol Microbiol 75:1513\u20131528","journal-title":"Mol Microbiol"},{"key":"701_CR44","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1128\/IAI.01747-07","volume":"76","author":"A Martner","year":"2008","unstructured":"Martner A, Dahlgren C, Paton JC, Wold AE (2008) Pneumolysin released during Streptococcus pneumoniae autolysis is a potent activator of intracellular oxygen radical production in neutrophils. Infect Immun 76:4079\u20134087","journal-title":"Infect Immun"},{"key":"701_CR45","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1128\/JB.188.5.1959-1968.2006","volume":"188","author":"T Mascher","year":"2006","unstructured":"Mascher T, Heintz M, Zahner D, Merai M, Hakenbeck R (2006) The CiaRH system of Streptococcus pneumoniae prevents lysis during stress induced by treatment with cell wall inhibitors and by mutations in pbp2x involved in beta-lactam resistance. J Bacteriol 188:1959\u20131968","journal-title":"J Bacteriol"},{"key":"701_CR46","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1128\/IAI.00811-09","volume":"78","author":"M Melin","year":"2010","unstructured":"Melin M, Di Paolo E, Tikkanen L, Jarva H, Neyt C, Kayhty H, Meri S, Poolman J, Vakevainen M (2010) Interaction of pneumococcal histidine triad proteins with human complement. Infect Immun 78:2089\u20132098","journal-title":"Infect Immun"},{"key":"701_CR47","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S1473-3099(14)71081-3","volume":"15","author":"MR Moore","year":"2015","unstructured":"Moore MR, Link-Gelles R, Schaffner W, Lynfield R, Lexau C, Bennett NM, Petit S, Zansky SM, Harrison LH, Reingold A, Miller L, Scherzinger K, Thomas A, Farley MM, Zell ER, Taylor TH Jr, Pondo T, Rodgers L, Mcgee L, Beall B, Jorgensen JH, Whitney CG (2015) Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis 15:301\u2013309","journal-title":"Lancet Infect Dis"},{"key":"701_CR48","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1086\/528375","volume":"197","author":"M Moschioni","year":"2008","unstructured":"Moschioni M, Donati C, Muzzi A, Masignani V, Censini S, Hanage WP, Bishop CJ, Reis JN, Normark S, Henriques-Normark B, Covacci A, Rappuoli R, Barocchi MA (2008) Streptococcus pneumoniae contains 3 rlrA pilus variants that are clonally related. J Infect Dis 197:888\u2013896","journal-title":"J Infect Dis"},{"key":"701_CR49","doi-asserted-by":"crossref","first-page":"7785","DOI":"10.1128\/JB.00673-06","volume":"188","author":"M Moscoso","year":"2006","unstructured":"Moscoso M, Garcia E, Lopez R (2006) Biofilm formation by Streptococcus pneumoniae: role of choline, extracellular DNA, and capsular polysaccharide in microbial accretion. J Bacteriol 188:7785\u20137795","journal-title":"J Bacteriol"},{"key":"701_CR50","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1128\/IAI.01475-06","volume":"75","author":"AL Nelson","year":"2007","unstructured":"Nelson AL, Roche AM, Gould JM, Chim K, Ratner AJ, Weiser JN (2007) Capsule enhances pneumococcal colonization by limiting mucus-mediated clearance. Infect Immun 75:83\u201390","journal-title":"Infect Immun"},{"key":"701_CR51","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/MMBR.00014-09","volume":"73","author":"AH Nobbs","year":"2009","unstructured":"Nobbs AH, Lamont RJ, Jenkinson HF (2009) Streptococcus adherence and colonization. Microbiol Mol Biol Rev 73:407\u2013450","journal-title":"Microbiol Mol Biol Rev"},{"key":"701_CR52","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0140-6736(09)61204-6","volume":"374","author":"KL Brien","year":"2009","unstructured":"Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, Mccall N, Lee E, Mulholland K, Levine OS, Cherian T, Hib & Pneumococcal Global Burden of Disease Study (2009) Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374:893\u2013902","journal-title":"Lancet"},{"key":"701_CR53","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1111\/j.1365-2958.2006.05310.x","volume":"61","author":"MR Oggioni","year":"2006","unstructured":"Oggioni MR, Trappetti C, Kadioglu A, Cassone M, Iannelli F, Ricci S, Andrew PW, Pozzi G (2006) Switch from planktonic to sessile life: a major event in pneumococcal pathogenesis. Mol Microbiol 61:1196\u20131210","journal-title":"Mol Microbiol"},{"key":"701_CR54","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1096\/fj.08-119537","volume":"23","author":"AD Ogunniyi","year":"2009","unstructured":"Ogunniyi AD, Grabowicz M, Mahdi LK, Cook J, Gordon DL, Sadlon TA, Paton JC (2009) Pneumococcal histidine triad proteins are regulated by the Zn2+-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H. FASEB J 23:731\u2013738","journal-title":"FASEB J"},{"key":"701_CR55","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1038\/srep02040","volume":"3","author":"L Pancotto","year":"2013","unstructured":"Pancotto L, De Angelis G, Bizzarri E, Barocchi MA, Del Giudice G, Moschioni M, Ruggiero P (2013) Expression of the Streptococcus pneumoniae pilus-1 undergoes on and off switching during colonization in mice. Sci Rep 3:2040","journal-title":"Sci Rep"},{"key":"701_CR56","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1128\/IAI.00228-09","volume":"77","author":"D Parker","year":"2009","unstructured":"Parker D, Soong G, Planet P, Brower J, Ratner AJ, Prince A (2009) The NanA neuraminidase of Streptococcus pneumoniae is involved in biofilm formation. Infect Immun 77:3722\u20133730","journal-title":"Infect Immun"},{"key":"701_CR57","doi-asserted-by":"crossref","first-page":"6815","DOI":"10.1128\/JB.185.23.6815-6825.2003","volume":"185","author":"CD Pericone","year":"2003","unstructured":"Pericone CD, Park S, Imlay JA, Weiser JN (2003) Factors contributing to hydrogen peroxide resistance in Streptococcus pneumoniae include pyruvate oxidase (SpxB) and avoidance of the toxic effects of the fenton reaction. J Bacteriol 185:6815\u20136825","journal-title":"J Bacteriol"},{"key":"701_CR58","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1046\/j.1365-2958.1996.501417.x","volume":"21","author":"EV Pestova","year":"1996","unstructured":"Pestova EV, Havarstein LS, Morrison DA (1996) Regulation of competence for genetic transformation in Streptococcus pneumoniae by an auto-induced peptide pheromone and a two-component regulatory system. Mol Microbiol 21:853\u2013862","journal-title":"Mol Microbiol"},{"key":"701_CR59","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S2352-4642(18)30168-8","volume":"2","author":"M Pichichero","year":"2018","unstructured":"Pichichero M, Kaur R, Scott DA, Gruber WC, Trammel J, Almudevar A, Center KJ (2018) Effectiveness of 13-valent pneumococcal conjugate vaccination for protection against acute otitis media caused by Streptococcus pneumoniae in healthy young children: a prospective observational study. Lancet Child Adolesc Health 2:561\u2013568","journal-title":"Lancet Child Adolesc Health"},{"key":"701_CR60","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1128\/IAI.02155-14","volume":"82","author":"CD Plumptre","year":"2014","unstructured":"Plumptre CD, Hughes CE, Harvey RM, Eijkelkamp BA, Mcdevitt CA, Paton JC (2014) Overlapping functionality of the Pht proteins in zinc homeostasis of Streptococcus pneumoniae. Infect Immun 82:4315\u20134324","journal-title":"Infect Immun"},{"key":"701_CR61","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1001\/jama.295.14.1668","volume":"295","author":"KA Poehling","year":"2006","unstructured":"Poehling KA, Talbot TR, Griffin MR, Craig AS, Whitney CG, Zell E, Lexau CA, Thomas AR, Harrison LH, Reingold AL, Hadler JL, Farley MM, Anderson BJ, Schaffner W (2006) Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine. JAMA 295:1668\u20131674","journal-title":"JAMA"},{"key":"701_CR62","doi-asserted-by":"crossref","first-page":"E3421","DOI":"10.1073\/pnas.1424144112","volume":"112","author":"P Rai","year":"2015","unstructured":"Rai P, Parrish M, Tay IJ, Li N, Ackerman S, He F, Kwang J, Chow VT, Engelward BP (2015) Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells. Proc Natl Acad Sci USA 112:E3421\u2013E3430","journal-title":"Proc Natl Acad Sci USA"},{"key":"701_CR63","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.1016\/j.vaccine.2010.04.042","volume":"28","author":"G Regev-Yochay","year":"2010","unstructured":"Regev-Yochay G, Hanage WP, Trzcinski K, Rifas-Shiman SL, Lee G, Bessolo A, Huang SS, Pelton SI, Mcadam AJ, Finkelstein JA, Lipsitch M, Malley R (2010) Re-emergence of the type 1 pilus among Streptococcus pneumoniae isolates in Massachusetts, USA. Vaccine 28:4842\u20134846","journal-title":"Vaccine"},{"key":"701_CR64","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1086\/381547","volume":"38","author":"G Regev-Yochay","year":"2004","unstructured":"Regev-Yochay G, Raz M, Dagan R, Porat N, Shainberg B, Pinco E, Keller N, Rubinstein E (2004) Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. Clin Infect Dis 38:632\u2013639","journal-title":"Clin Infect Dis"},{"key":"701_CR65","doi-asserted-by":"crossref","first-page":"6532","DOI":"10.1128\/JB.00813-07","volume":"189","author":"G Regev-Yochay","year":"2007","unstructured":"Regev-Yochay G, Trzcinski K, Thompson CM, Lipsitch M, Malley R (2007) SpxB is a suicide gene of Streptococcus pneumoniae and confers a selective advantage in an in vivo competitive colonization model. J Bacteriol 189:6532\u20136539","journal-title":"J Bacteriol"},{"key":"701_CR66","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1093\/cid\/ciy750","volume":"68","author":"D Ren","year":"2019","unstructured":"Ren D, Xu Q, Almudevar AL, Pichichero ME (2019) Impaired proinflammatory response in stringently defined otitis-prone children during viral upper respiratory infections. Clin Infect Dis 68:1566\u20131574","journal-title":"Clin Infect Dis"},{"key":"701_CR67","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1086\/589775","volume":"198","author":"L Rose","year":"2008","unstructured":"Rose L, Shivshankar P, Hinojosa E, Rodriguez A, Sanchez CJ, Orihuela CJ (2008) Antibodies against PsrP, a novel Streptococcus pneumoniae adhesin, block adhesion and protect mice against pneumococcal challenge. J Infect Dis 198:375\u2013383","journal-title":"J Infect Dis"},{"key":"701_CR68","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/j.1365-2958.1997.mmi494.x","volume":"25","author":"C Rosenow","year":"1997","unstructured":"Rosenow C, Ryan P, Weiser JN, Johnson S, Fontan P, Ortqvist A, Masure HR (1997) Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol Microbiol 25:819\u2013829","journal-title":"Mol Microbiol"},{"issue":"884\u201391","key":"701_CR69","first-page":"e6","volume":"25","author":"HM Rowe","year":"2019","unstructured":"Rowe HM, Karlsson E, Echlin H, Chang TC, Wang L, Van Opijnen T, Pounds SB, Schultz-Cherry S, Rosch JW (2019) Bacterial factors required for transmission of Streptococcus pneumoniae in mammalian hosts. Cell Host Microbe 25(884\u201391):e6","journal-title":"Cell Host Microbe"},{"key":"701_CR70","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fcimb.2019.00094","volume":"9","author":"G Salvadori","year":"2019","unstructured":"Salvadori G, Junges R, Morrison DA, Petersen FC (2019) Competence in Streptococcus pneumoniae and close commensal relatives: mechanisms and implications. Front Cell Infect Microbiol 9:94","journal-title":"Front Cell Infect Microbiol"},{"key":"701_CR71","doi-asserted-by":"crossref","first-page":"e1001044","DOI":"10.1371\/journal.ppat.1001044","volume":"6","author":"CJ Sanchez","year":"2010","unstructured":"Sanchez CJ, Shivshankar P, Stol K, Trakhtenbroit S, Sullam PM, Sauer K, Hermans PW, Orihuela CJ (2010) The pneumococcal serine-rich repeat protein is an intra-species bacterial adhesin that promotes bacterial aggregation in vivo and in biofilms. PLoS Pathog 6:e1001044","journal-title":"PLoS Pathog"},{"key":"701_CR72","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.ijporl.2014.06.024","volume":"78","author":"PA Schachern","year":"2014","unstructured":"Schachern PA, Tsuprun V, Ferrieri P, Briles DE, Goetz S, Cureoglu S, Paparella MM, Juhn S (2014) Pneumococcal PspA and PspC proteins: potential vaccine candidates for experimental otitis media. Int J Pediatr Otorhinolaryngol 78:1517\u20131521","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"701_CR73","doi-asserted-by":"crossref","unstructured":"Schnyder S, Little BA, Croucher NJ, Pelton SI, Sabharwal V (2014) Lack of middle ear virulence of Streptococcus pneumoniae 33F isolates in chinchillas is associated with absence of the PsrP Pathogenicity Island. IDWeek 2014, Meeting of the Infectious Diseases Society of America.","DOI":"10.1093\/ofid\/ofu051.06"},{"key":"701_CR74","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1471-2180-11-75","volume":"11","author":"C Trappetti","year":"2011","unstructured":"Trappetti C, Gualdi L, Di Meola L, Jain P, Korir CC, Edmonds P, Iannelli F, Ricci S, Pozzi G, Oggioni MR (2011) The impact of the competence quorum sensing system on Streptococcus pneumoniae biofilms varies depending on the experimental model. BMC Microbiol 11:75","journal-title":"BMC Microbiol"},{"key":"701_CR75","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1128\/IAI.05644-11","volume":"79","author":"C Trappetti","year":"2011","unstructured":"Trappetti C, Potter AJ, Paton AW, Oggioni MR, Paton JC (2011) LuxS mediates iron-dependent biofilm formation, competence, and fratricide in Streptococcus pneumoniae. Infect Immun 79:4550\u20134558","journal-title":"Infect Immun"},{"key":"701_CR76","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1128\/IAI.67.9.4720-4724.1999","volume":"67","author":"AH Tu","year":"1999","unstructured":"Tu AH, Fulgham RL, Mccrory MA, Briles DE, Szalai AJ (1999) Pneumococcal surface protein A inhibits complement activation by Streptococcus pneumoniae. Infect Immun 67:4720\u20134724","journal-title":"Infect Immun"},{"key":"701_CR77","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1128\/IAI.01096-12","volume":"81","author":"JE Vidal","year":"2013","unstructured":"Vidal JE, Howery KE, Ludewick HP, Nava P, Klugman KP (2013) Quorum-sensing systems LuxS\/autoinducer 2 and Com regulate Streptococcus pneumoniae biofilms in a bioreactor with living cultures of human respiratory cells. Infect Immun 81:1341\u20131353","journal-title":"Infect Immun"},{"key":"701_CR78","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1128\/IAI.05186-11","volume":"79","author":"JE Vidal","year":"2011","unstructured":"Vidal JE, Ludewick HP, Kunkel RM, Zahner D, Klugman KP (2011) The LuxS-dependent quorum-sensing system regulates early biofilm formation by Streptococcus pneumoniae strain D39. Infect Immun 79:4050\u20134060","journal-title":"Infect Immun"},{"key":"701_CR79","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.4049\/jimmunol.1402518","volume":"196","author":"MM Walker","year":"2016","unstructured":"Walker MM, Novak L, Widener R, Grubbs JA, King J, Hale JY, Ochs MM, Myers LE, Briles DE, Deshane J (2016) PcpA promotes higher levels of infection and modulates recruitment of myeloid-derived suppressor cells during pneumococcal pneumonia. J Immunol 196:2239\u20132248","journal-title":"J Immunol"},{"key":"701_CR80","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1128\/IAI.00006-14","volume":"82","author":"W Wang","year":"2014","unstructured":"Wang W, Zhou A, Zhang X, Xiang Y, Huang Y, Wang L, Zhang S, Liu Y, Yin Y, He Y (2014) Interleukin 17A promotes pneumococcal clearance by recruiting neutrophils and inducing apoptosis through a p38 mitogen-activated protein kinase-dependent mechanism in acute otitis media. Infect Immun 82:2368\u20132377","journal-title":"Infect Immun"},{"key":"701_CR81","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1128\/IAI.62.6.2582-2589.1994","volume":"62","author":"JN Weiser","year":"1994","unstructured":"Weiser JN, Austrian R, Sreenivasan PK, Masure HR (1994) Phase variation in pneumococcal opacity: relationship between colonial morphology and nasopharyngeal colonization. Infect Immun 62:2582\u20132589","journal-title":"Infect Immun"},{"key":"701_CR82","first-page":"e01044","volume":"85","author":"JT Wren","year":"2017","unstructured":"Wren JT, Blevins LK, Pang B, Basu Roy A, Oliver MB, Reimche JL, Wozniak JE, Alexander-Miller MA, Swords WE (2017) Pneumococcal neuraminidase A (NanA) promotes biofilm formation and synergizes with influenza a virus in nasal colonization and middle ear infection. Infect Immun 85:e01044-e1116","journal-title":"Infect Immun"},{"issue":"487","key":"701_CR83","first-page":"e1","volume":"23","author":"Q Xu","year":"2017","unstructured":"Xu Q, Casey JR, Almudevar A, Pichichero ME (2017) Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children. Clin Microbiol Infect 23(487):e1-87","journal-title":"Clin Microbiol Infect"},{"key":"701_CR84","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fcimb.2018.00138","volume":"8","author":"MK Yadav","year":"2018","unstructured":"Yadav MK, Vidal JE, Go YY, Kim SH, Chae SW, Song JJ (2018) The LuxS\/AI-2 Quorum-sensing system of Streptococcus pneumoniae Is Required to cause disease, and to regulate virulence- and metabolism-related genes in a rat model of middle ear infection. Front Cell Infect Microbiol 8:138","journal-title":"Front Cell Infect Microbiol"},{"key":"701_CR85","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3389\/fcimb.2019.00301","volume":"9","author":"M Yamaguchi","year":"2019","unstructured":"Yamaguchi M, Hirose Y, Takemura M, Ono M, Sumitomo T, Nakata M, Terao Y, Kawabata S (2019) Streptococcus pneumoniae Evades Host Cell phagocytosis and limits host mortality through its cell wall anchoring protein PfbA. Front Cell Infect Microbiol 9:301","journal-title":"Front Cell Infect Microbiol"},{"key":"701_CR86","doi-asserted-by":"crossref","first-page":"36272","DOI":"10.1074\/jbc.M807087200","volume":"283","author":"M Yamaguchi","year":"2008","unstructured":"Yamaguchi M, Terao Y, Mori Y, Hamada S, Kawabata S (2008) PfbA, a novel plasmin- and fibronectin-binding protein of Streptococcus pneumoniae, contributes to fibronectin-dependent adhesion and antiphagocytosis. J Biol Chem 283:36272\u201336279","journal-title":"J Biol Chem"},{"key":"701_CR87","doi-asserted-by":"crossref","first-page":"6283","DOI":"10.1128\/AEM.68.12.6283-6291.2002","volume":"68","author":"A Yoshida","year":"2002","unstructured":"Yoshida A, Kuramitsu HK (2002) Multiple Streptococcus mutans genes are involved in biofilm formation. Appl Environ Microbiol 68:6283\u20136291","journal-title":"Appl Environ Microbiol"},{"key":"701_CR88","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.chom.2016.12.005","volume":"21","author":"MA Zafar","year":"2017","unstructured":"Zafar MA, Wang Y, Hamaguchi S, Weiser JN (2017) Host-to-Host Transmission of Streptococcus pneumoniae is driven by its inflammatory toxin, Pneumolysin. Cell Host Microbe 21:73\u201383","journal-title":"Cell Host Microbe"},{"key":"701_CR89","first-page":"1899","volume":"119","author":"Z Zhang","year":"2009","unstructured":"Zhang Z, Clarke TB, Weiser JN (2009) Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Investig 119:1899\u20131909","journal-title":"J Clin Investig"}],"container-title":["Medical Microbiology and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00430-021-00701-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00430-021-00701-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00430-021-00701-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T18:04:46Z","timestamp":1621533886000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00430-021-00701-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":89,"journal-issue":{"issue":"2-3","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["701"],"URL":"https:\/\/doi.org\/10.1007\/s00430-021-00701-w","relation":{},"ISSN":["0300-8584","1432-1831"],"issn-type":[{"value":"0300-8584","type":"print"},{"value":"1432-1831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"5 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}