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Vol. 16, Issue 1, 396-404, January 2005

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Mycobacterium tuberculosis Functional Network Analysis by Global Subcellular Protein Profiling

Kwasi G. Mawuenyega ^*, Christian V. Forst , Karen M. Dobos , John T. Belisle , Jin Chen , E. Morton Bradbury ^* , Andrew R.M. Bradbury , and Xian Chen ^* ||

^* Cell Biology, Structural Biology, and Flow Cytometry, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545; Molecular Microbiology and Immunology, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545; Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology Laboratory, Colorado State University, Ft. Collins, CO 80523; and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA 95616

Submitted April 21, 2004; Revised September 13, 2004; Accepted October 17, 2004
Monitoring Editor: Keith Yamamoto

Trends in increased tuberculosis infection and a fatality rate of 23% have necessitated the search for alternative biomarkers using newly developed postgenomic approaches. Here we provide a systematic analysis of Mycobacterium tuberculosis (Mtb) by directly profiling its gene products. This analysis combines high-throughput proteomics and computational approaches to elucidate the globally expressed complements of the three subcellular compartments (the cell wall, membrane, and cytosol) of Mtb. We report the identifications of 1044 proteins and their corresponding localizations in these compartments. Genome-based computational and metabolic pathways analyses were performed and integrated with proteomics data to reconstruct response networks. From the reconstructed response networks for fatty acid degradation and lipid biosynthesis pathways in Mtb, we identified proteins whose involvements in these pathways were not previously suspected. Furthermore, the subcellular localizations of these expressed proteins provide interesting insights into the compartmentalization of these pathways, which appear to traverse from cell wall to cytoplasm. Results of this large-scale subcellular proteome profile of Mtb have confirmed and validated the computational network hypothesis that functionally related proteins work together in larger organizational structures.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

^|| Corresponding author. E-mail address: chen_xian{at}lanl.gov.

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