Pneumococcal histidine triad proteins are regulated by the Zn2+-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H

Ogunniyi, Abiodun D. and Grabowicz, Marcin and Mahdi, Layla K. and Cook, Jan and Gordon, David L. and Sadlon, Tania A. and Paton, James C. (2009) Pneumococcal histidine triad proteins are regulated by the Zn2+-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H. The FASEB Journal, 23 (3). pp. 731-738. ISSN 0892-6638

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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Restricted access to published version in accordance with the copyright policy of the publisher.
Faculty / Department / School: Historic - Faculty of Sciences - No Department
Date Deposited: 23 Nov 2016 03:13
Last Modified: 03 May 2018 03:09
Uncontrolled Keywords: Streptococcus pneumonia; virulence; gene expression, innate immunity; protein vaccines
Fields of Research : 06 Biological Sciences > 0605 Microbiology > 060501 Bacteriology
11 Medical and Health Sciences > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry
11 Medical and Health Sciences > 1108 Medical Microbiology > 110801 Medical Bacteriology
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Funding Details:
Identification Number or DOI: 10.1096/fj.08-119537
URI: http://eprints.usq.edu.au/id/eprint/28824

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