{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:07:33Z","timestamp":1789380453079,"version":"build-2803163510"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"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":[[2011,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Avirulent strains of a bacterial pathogen could be useful tools for investigating immunological responses to infection and potentially effective vaccines. We have therefore constructed an auxotrophic TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            strain of\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            by deleting the\n            <jats:italic>pabB<\/jats:italic>\n            gene Sp_0665. The TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            strain grew well in complete medium but was unable to grow in serum unless it was supplemented with\n            <jats:italic>para<\/jats:italic>\n            -aminobenzoic acid (PABA). The TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            strain was markedly attenuated in virulence in mouse models 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            nasopharyngeal colonization, pneumonia, and sepsis. Supplementing mouse drinking water with PABA largely restored the virulence of TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            . An additional \u0394\n            <jats:italic>pab<\/jats:italic>\n            strain constructed in the D39 capsular serotype 2 background was also avirulent in a sepsis model. Systemic inoculation of mice with TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            induced antibody responses to\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            protein antigens, including PpmA, PsaA, pneumolysin, and CbpD, but not capsular polysaccharide. Flow cytometry demonstrated that IgG in sera from TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            -vaccinated mice bound to the surface of TIGR4 and D39 bacteria but not to a capsular serotype 3 strain, strain 0100993. Mice vaccinated with the TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            or D39 \u0394\n            <jats:italic>pab<\/jats:italic>\n            strain by intraperitoneal inoculation were protected from developing septicemia when challenged with the homologous\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            strain. Vaccination with the TIGR4 \u0394\n            <jats:italic>pab<\/jats:italic>\n            strain provided only weak or no protection against heterologous challenge with the D39 or 0100993 strain but did strongly protect against a TIGR4 capsular-switch strain expressing a serotype 2 capsule. The failure of cross-protection after systemic vaccination with \u0394\n            <jats:italic>pab<\/jats:italic>\n            bacteria suggests that parenteral administration of a live attenuated vaccine is not an attractive approach for preventing\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            infection.\n          <\/jats:p>","DOI":"10.1128\/iai.05923-11","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T06:11:42Z","timestamp":1317103902000},"page":"4965-4976","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Infection with Conditionally Virulent Streptococcus pneumoniae \u0394\n            <i>pab<\/i>\n            Strains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains"],"prefix":"10.1128","volume":"79","author":[{"given":"Suneeta","family":"Chimalapati","sequence":"first","affiliation":[{"name":"Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London WC1E 6JF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cohen","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London WC1E 6JF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Camberlein","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London WC1E 6JF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Durmort","sequence":"additional","affiliation":[{"name":"CEA, Grenoble 1, Institut de Biologie Structurale Jean-Pierre Ebel, Grenoble, 41 Rue Jules Horowitz, 38027, Grenoble Cedex 1, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Baxendale","sequence":"additional","affiliation":[{"name":"Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge CB23 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corn\u00e9","family":"de Vogel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"van Belkum","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London WC1E 6JF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.09.026"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.5.2526-2534.2002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10114"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/376571"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01953.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.2.549-557.1998"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01400-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.16.5317-5323.1992"},{"key":"e_1_3_2_10_2","first-page":"1389","article-title":"Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors","volume":"45","author":"Hava D. 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