Journal
TUBERCULOSIS
Volume 84, Issue 3-4, Pages 218-227Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.tube.2004.02.003
Keywords
Mycobacterium tuberculosis; stationary phase; dormancy; microarray
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Funding
- NIAID NIH HHS [AI 44826] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI044826] Funding Source: NIH RePORTER
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The innate mechanisms used by Mycobacterium tuberculosis to persist during periods of non-proliferation are central to understanding the physiology of the bacilli during latent disease. We have used whole genome expression profiling to expose adaptive mechanisms initiated by M. tuberculosis in two common models of M. tuberculosis non-proliferation. The first of these models was a standard growth curve in which gene expression changes were followed from exponential growth through the transition to stationary phase. In the second model, we followed the adaptive process of M. tuberculosis during transition from aerobic growth to a state of anaerobic non-replicating persistence. The most striking finding from these experiments was the strong induction of the entire DosR dormancy regulon over approximately 20 days during the long transition to an anaerobic state. This is contrasted by the muted overall response to aerated stationary phase with only a partial dormancy regulon response. From the results presented here we conclude that the respiration-limited environment of the oxygen-depleted NRP model recreates at least one fundamental factor for which the genome of M. tuberculosis encodes a decisive adaptive program. (C) 2004 Elsevier Ltd. All rights reserved.
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