Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/54179
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Type: Journal article
Title: Pneumococcal histidine triad proteins are regulated by the Zn²⁺-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H
Other Titles: Pneumococcal histidine triad proteins are regulated by the Zn(2+)-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H
Author: Ogunniyi, A.
Grabowicz, M.
Mahdi, L.
Cook, J.
Gordon, D.
Sadlon, T.
Paton, J.
Citation: The FASEB Journal, 2009; 2008(3):1-8
Publisher: Federation Amer Soc Exp Biol
Issue Date: 2009
ISSN: 0892-6638
1530-6860
Statement of
Responsibility: 
Abiodun D. Ogunniyi, Marcin Grabowicz, Layla K. Mahdi, Jan Cook, David L. Gordon, Tania A. Sadlon and James C. Paton
Abstract: 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 Streptococcus pneumoniae D39. In either challenge model, mutagenesis of all 4 genes was required to completely abolish virulence relative to the wild-type, suggesting significant functional redundancy among Pht proteins. The in vivo expression of pht genes was significantly up-regulated in the nasopharynx and lungs compared with blood. We provide unequivocal molecular evidence for Zn²⁺-dependent, AdcR-mediated, regulation of pht gene expression by real-time reverse transcriptase-polymerase chain reaction, Western blotting, and electrophoretic mobility-shift 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.—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 Zn²⁺-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H.
Keywords: Streptococcus pneumoniae
virulence
gene expression
innate immunity
protein vaccines
Rights: © 2009 by The Federation of American Societies for Experimental Biology.
DOI: 10.1096/fj.08-119537
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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