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J. Bacteriol. doi:10.1128/JB.01787-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of mycobacteria to survival inside the macrophage

D. J. V. Beste, E. Laing, B. Bonde, C. Avignone-Rossa, M. E. Bushell, and J. J. McFadden*

School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, United Kingdom

* To whom correspondence should be addressed. Email: j.mcfadden{at}surrey.ac.uk.


   Abstract

The adaptation of the tubercle bacillus to the host environment is likely to involve a complex set of gene regulatory events and physiological switches in response to environmental signals. In order to deconstruct the physiological state of Mycobacterium tuberculosis in vivo we used a chemostat model to study a single aspect of the organism's in vivo state: slow growth. Mycobacterium bovis BCG was cultivated at fast and slow growth rates in a carbon-limited chemostat and transcriptomic analysis performed to identify the gene regulatory events associated with slow growth. The results demonstrated that slow growth was associated with the induction of several genes of the dormancy survival regulon. There was also a striking overlap between the transcriptomic profile of BCG in the chemostat model and the response of M. tuberculosis to growth in the macrophage implying that a significant component of the response of the pathogen to the macrophage environment is the response to slow-growth in carbon-limited conditions. This demonstrated the importance of adaptation to slow growth rate to the virulence strategy of M. tuberculosis and also the value of the chemostat model for deconstructing components of the in vivo state of this important pathogen.




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