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Infection and Immunity, February 2006, p. 1233-1242, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1233-1242.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Unique Transcriptome Signature of Mycobacterium tuberculosis in Pulmonary Tuberculosis{dagger}

Helmy Rachman,1 Michael Strong,2 Timo Ulrichs,1 Leander Grode,1 Johannes Schuchhardt,3 Hans Mollenkopf,1 George A. Kosmiadi,4 David Eisenberg,2 and Stefan H. E. Kaufmann1*

Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany,1 Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, California,2 MicroDiscovery GmbH, Berlin, Germany,3 Central Tuberculosis Research Institute, Department of Immunology 2, Moscow, Russian Federation4

Received 28 April 2005/ Returned for modification 15 June 2005/ Accepted 8 November 2005

Although tuberculosis remains a substantial global threat, the mechanisms that enable mycobacterial persistence and replication within the human host are ill defined. This study represents the first genome-wide expression analysis of Mycobacterium tuberculosis from clinical lung samples, which has enabled the identification of M. tuberculosis genes actively expressed during pulmonary tuberculosis. To obtain optimal information from our DNA array analyses, we analyzed the differentially expressed genes within the context of computationally inferred protein networks. Protein networks were constructed using functional linkages established by the Rosetta stone, phylogenetic profile, conserved gene neighbor, and operon computational methods. This combined approach revealed that during pulmonary tuberculosis, M. tuberculosis actively transcribes a number of genes involved in active fortification and evasion from host defense systems. These genes may provide targets for novel intervention strategies.

* Corresponding author. Mailing address: Max Planck Institute for Infection, Immunology, Schumannstrasse 21-22, Berlin 10117, Germany. Phone: 49-30-28460500. Fax: 49-30-28460501. E-mail: kaufmann{at}mpiib-berlin.mpg.de.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. L. Flynn

Infection and Immunity, February 2006, p. 1233-1242, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1233-1242.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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