{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:57:20Z","timestamp":1792670240592,"version":"4.5.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            is a leading cause of human diseases such as pneumonia, bacteremia, meningitis, and otitis media. Pneumolysin (Ply) is an important virulence factor of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pneumoniae<\/jats:named-content>\n            and a promising future vaccine target. However, the expansion of clones carrying\n            <jats:italic>ply<\/jats:italic>\n            alleles with reduced hemolytic activity has been observed in serotypes associated with outbreaks of invasive disease and includes an allele identified in a highly virulent serotype 1 isolate (\n            <jats:italic>ply<\/jats:italic>\n            4496). The virulence of Ply-deficient and\n            <jats:italic>ply<\/jats:italic>\n            allelic-replacement derivatives of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. pneumoniae<\/jats:named-content>\n            D39 was compared with that of wild-type D39. In addition, the protective immunogenicity of Ply against pneumococci with low versus high hemolytic activity was also investigated. Replacement of D39\n            <jats:italic>ply<\/jats:italic>\n            with\n            <jats:italic>ply<\/jats:italic>\n            4496 resulted in a small but statistically significant reduction of virulence. However, both native Ply- and Ply4496-expressing strains were significantly more virulent than a Ply-deficient mutant. While the numbers of both Ply- and Ply4496-expressing isolate cells were higher in the blood than the numbers of Ply-deficient mutant cells, the growth of the Ply4496-expressing strain was superior to that of the wild type in the first 15 h postchallenge. Ply immunization provided protection regardless of the hemolytic activity of the challenge strain. In summary, we show that low-hemolytic-activity Ply alleles contribute to systemic virulence and may provide a survival advantage in the blood. Moreover, pneumococci expressing such alleles remain vulnerable to Ply-based vaccines.\n          <\/jats:p>","DOI":"10.1128\/iai.05418-11","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T02:45:19Z","timestamp":1311648319000},"page":"4122-4130","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Pneumolysin with Low Hemolytic Activity Confers an Early Growth Advantage to Streptococcus pneumoniae in the Blood"],"prefix":"10.1128","volume":"79","author":[{"given":"Richard M.","family":"Harvey","sequence":"first","affiliation":[{"name":"Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abiodun D.","family":"Ogunniyi","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austen Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Paton","sequence":"additional","affiliation":[{"name":"Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.12.5683-5688.1994"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2008.00518.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.448-455.1995"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.5.1969-1974.1995"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.7.2037-2042.1989"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.8.3750-3756.1999"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.11.4966-4970.2003"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/318536"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.02.014"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5454-5461.2002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019650"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(93)17067-F"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.4.1501-1503.1994"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/520091"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.4.1813-1819.2003"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.492-501.2000"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.44.1.151-159.2006"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.1.586-593.2006"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900025"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1996.0044"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0435928100"},{"key":"e_1_3_2_24_2","first-page":"293","article-title":"The recA gene of Streptococcus pneumoniae is part of a competence-induced operon and controls an SOS regulon","volume":"85","author":"Martin B.","year":"1995","unstructured":"MartinB.GarciaP.CastanieM. 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