Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 179K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Meghji, S. Articles by Coates, A. R.M. Search for Related Content PubMed PubMed Citation Articles by Meghji, S. Articles by Coates, A. R.M. Social Bookmarking                            What's this?

Articles

Sajeda Meghji^*, Peter A. White^*, Sean P. Nair^*, Krisanavane Reddi^*, Kyle Heron^*, Brian Henderson^*, Andrea Zaliani, Gianluca Fossati, Paolo Mascagni, John F. Hunt^||, Michael M. Roberts^¶, and Anthony R.M. Coates^¶

From the ^* Maxillofacial Surgery Research Unit, Eastman Dental Institute, University College London, London WC1X 8LD, United Kingdom; Italfarmaco SpA, Centro Richerche, 20092 Cinisello B (MI), Italy; Molecular Immunology Division, National Institute for Medical Research, London NW7 1AA, United Kingdom; ^|| Howard Hughes Medical Institute, The University of Texas, Southwestern Medical Center, Dallas, Texas 75235; and ^¶ Division of Molecular Microbiology, St. George's Hospital Medical School, London SW17 0RE, United Kingdom

Pott's disease (spinal tuberculosis), a condition characterized by massive resorption of the spinal vertebrae, is one of the most striking pathologies resulting from local infection with Mycobacterium tuberculosis (Mt; Boachie-Adjei, O., and R.G. Squillante. 1996. Orthop. Clin. North Am. 27:95–103). The pathogenesis of Pott's disease is not established. Here we report for the first time that a protein, identified by a monoclonal antibody to be the Mt heat shock protein (Baird, P.N., L.M. Hall, and A.R.M. Coates. 1989. J. Gen. Microbiol. 135:931–939) chaperonin (cpn) 10, is responsible for the osteolytic activity of this bacterium. Recombinant Mt cpn10 is a potent stimulator of bone resorption in bone explant cultures and induces osteoclast recruitment, while inhibiting the proliferation of an osteoblast bone–forming cell line. Furthermore, we have found that synthetic peptides corresponding to sequences within the flexible loop and sequence 65–70 of Mt cpn10 may comprise a single conformational unit which encompasses its potent bone-resorbing activity. Our findings suggest that Mt cpn10 may be a valuable pharmacological target for the clinical therapy of vertebral tuberculosis and possibly other bone diseases.

¹ Abbreviations used in this paper: cpn, chaperonin; LAM, lipoarabinomannan; Mt, Mycobacterium tuberculosis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Hu, Y., Henderson, B., Lund, P. A., Tormay, P., Ahmed, M. T., Gurcha, S. S., Besra, G. S., Coates, A. R. M. (2008). A Mycobacterium tuberculosis Mutant Lacking the groEL Homologue cpn60.1 Is Viable but Fails To Induce an Inflammatory Response in Animal Models of Infection. Infect. Immun. 76: 1535-1546 [Abstract] [Full Text]  
• Henderson, B., Allan, E., Coates, A. R. M. (2006). Stress Wars: the Direct Role of Host and Bacterial Molecular Chaperones in Bacterial Infection. Infect. Immun. 74: 3693-3706 [Full Text]  
• Tormay, P., Coates, A. R. M., Henderson, B. (2005). The Intercellular Signaling Activity of the Mycobacterium tuberculosis Chaperonin 60.1 Protein Resides in the Equatorial Domain. J. Biol. Chem. 280: 14272-14277 [Abstract] [Full Text]  
• Saito, K., Ohara, N., Hotokezaka, H., Fukumoto, S., Yuasa, K., Naito, M., Fujiwara, T., Nakayama, K. (2004). Infection-induced Up-regulation of the Costimulatory Molecule 4-1BB in Osteoblastic Cells and Its Inhibitory Effect on M-CSF/RANKL-induced in Vitro Osteoclastogenesis. J. Biol. Chem. 279: 13555-13563 [Abstract] [Full Text]  
• Roberts, M. M., Coker, A. R., Fossati, G., Mascagni, P., Coates, A. R. M., Wood, S. P. (2003). Mycobacterium tuberculosis Chaperonin 10 Heptamers Self-Associate through Their Biologically Active Loops. J. Bacteriol. 185: 4172-4185 [Abstract] [Full Text]  
• Fossati, G., Izzo, G., Rizzi, E., Gancia, E., Modena, D., Moras, M. L., Niccolai, N., Giannozzi, E., Spiga, O., Bono, L., Marone, P., Leone, E., Mangili, F., Harding, S., Errington, N., Walters, C., Henderson, B., Roberts, M. M., Coates, A. R. M., Casetta, B., Mascagni, P. (2003). Mycobacterium tuberculosis Chaperonin 10 Is Secreted in the Macrophage Phagosome: Is Secretion Due to Dissociation and Adoption of a Partially Helical Structure at the Membrane?. J. Bacteriol. 185: 4256-4267 [Abstract] [Full Text]  
• Smith, I. (2003). Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence. Clin. Microbiol. Rev. 16: 463-496 [Abstract] [Full Text]  
• Lewthwaite, J. C., Coates, A. R. M., Tormay, P., Singh, M., Mascagni, P., Poole, S., Roberts, M., Sharp, L., Henderson, B. (2001). Mycobacterium tuberculosis Chaperonin 60.1 Is a More Potent Cytokine Stimulator than Chaperonin 60.2 (Hsp 65) and Contains a CD14-Binding Domain. Infect. Immun. 69: 7349-7355 [Abstract] [Full Text]  
• Kempsell, K. E., Cox, C. J., McColm, A. A., Bagshaw, J. A., Reece, R., Veale, D. J., Emery, P., Isaacs, J. D., Gaston, J. S. H., Crowe, J. S. (2001). Detection of Mycobacterium tuberculosis Group Organisms in Human and Mouse Joint Tissue by Reverse Transcriptase PCR: Prevalence in Diseased Synovial Tissue Suggests Lack of Specific Association with Rheumatoid Arthritis. Infect. Immun. 69: 1821-1831 [Abstract] [Full Text]  
• Henderson, B., Wilson, M. (1998). Commensal Communism and the Oral Cavity. JDR 77: 1674-1683 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS