Unique transcriptome signature of Mycobacterium tuberculosis in pulmonary tuberculosis.
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.
Rachman
Helmy
H
Max Planck Institute for Infection, Immunology, Schumannstrasse 21-22, Berlin 10117, Germany.
Strong
Michael
M
Ulrichs
Timo
T
Grode
Leander
L
Schuchhardt
Johannes
J
Mollenkopf
Hans
H
Kosmiadi
George A
GA
Eisenberg
David
D
Kaufmann
Stefan H E
SH
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000601:surgery; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome; D014158:Transcription, Genetic; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology / Q000601:surgery; D014397:Tuberculosis, Pulmonary / Q000382:microbiology* / Q000601:surgery
D001426:Bacterial Proteins; D020543:Proteome