{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:04:31Z","timestamp":1791263071181,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,10,29]],"date-time":"2008-10-29T00:00:00Z","timestamp":1225238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p>\n                    The pneumococcal histidine triad (Pht) proteins are a recently recognized family of surface proteins, comprising 4 members: PhtA, PhtB, PhtD, and PhtE. They are being promoted for inclusion in a multicomponent pneumococcal protein vaccine currently under development, but to date, their biological functions and their relative contributions to pathogenesis have not been clarified. In this study, the involvement of these proteins in pneumococcal virulence was investigated in murine models of sepsis and pneumonia by using defined, nonpolar mutants of the respective genes in\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    D39. In either challenge model, mutagenesis of all 4 genes was required to completely abolish virulence relative to the wild\u2010type, suggesting significant functional redundancy among Pht proteins. The\n                    <jats:italic>in vivo<\/jats:italic>\n                    expression of\n                    <jats:italic>pht<\/jats:italic>\n                    genes was significantly up\u2010regulated in the nasopharynx and lungs compared with blood. We provide unequivocal molecular evidence for Zn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent, AdcR\u2010mediated, regulation of\n                    <jats:italic>pht<\/jats:italic>\n                    gene expression by real\u2010time reverse transcriptase\u2010polymerase chain reaction, Western blotting, and electrophoretic mobility\u2010shift assays. We also present the first direct evidence for the biological function of this protein family by demonstrating that Pht proteins are required for inhibition of complement deposition on the pneumococcal surface through the recruitment of complement factor H.\u2014 Ogunniyi, A. D., Grabowicz, M., Mahdi, L. K., Cook, J., Gordon, D. L., Sadlon, T. A., Paton, J. C. Pneumococcal histidine triad proteins are regulated by the Zn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 731\u2013738 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-119537","type":"journal-article","created":{"date-parts":[[2008,10,29]],"date-time":"2008-10-29T20:46:39Z","timestamp":1225313199000},"page":"731-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Pneumococcal histidine triad proteins are regulated by the Zn\n                    <sup>2+<\/sup>\n                    \u2010dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H"],"prefix":"10.1096","volume":"23","author":[{"given":"Abiodun D.","family":"Ogunniyi","sequence":"first","affiliation":[{"name":"School of Molecular and Biomedical Science University of Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Grabowicz","sequence":"additional","affiliation":[{"name":"School of Molecular and Biomedical Science University of Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layla K","family":"Mahdi","sequence":"additional","affiliation":[{"name":"School of Molecular and Biomedical Science University of Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Cook","sequence":"additional","affiliation":[{"name":"School of Molecular and Biomedical Science University of Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Infectious Diseases Flinders Medical Centre and Flinders University of South Australia South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania A.","family":"Sadlon","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Infectious Diseases Flinders Medical Centre and Flinders University of South Australia South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Paton","sequence":"additional","affiliation":[{"name":"School of Molecular and Biomedical Science University of Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0403-390"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-925524"},{"key":"e_1_2_6_4_1","first-page":"382","volume-title":"The Pneumococcus","author":"Paton J. 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