E-BUGS-83 - Transcription profiling of Mycobacterium bovis to determine genetic requirements for fast and slow growth in Mycobacteria

Status
Released on 28 April 2009, last updated on 1 May 2014
Organism
Mycobacterium bovis
Samples (4)
Arrays (2)
Protocols (9)
Description
Mycobacterium tuberculosis infects a third of the world's population. Primary tuberculosis involving active fast bacterial replication is often followed by asymptomatic latent tuberculosis, which is characterised by slow or non-replicating bacteria. Reactivation of the latent infection involving a switch back to active bacterial replication can lead to post-primary transmissible tuberculosis. Mycobacterial mechanisms involved in slow growth or switching growth rate provide rational targets for the development of new drugs against persistent mycobacterial infection. Using chemostat culture to control growth rate we screened a transposon mutant library by Transposon site hybridization (TraSH) selection to define the genetic requirements for slow and fast growth of Mycobacterium bovis (BCG) and for the requirements of switching growth rate. We identified 84 genes that are exclusively required for slow growth (69 hours doubling time) and 256 genes required for switching from slow to fast growth. To validate these findings we performed experiments using individual M. tuberculosis and M. bovis BCG knock out mutants. We have demonstrated that growth rate control is a carefully orchestrated process which requires a distinct set of genes encoding several virulence determinants, gene regulators and metabolic enzymes. The mce1 locus appears to be a component of the switch to slow growth rate, which is consistent with the proposed role in virulence of M. tuberculosis. These results suggest novel perspectives for unravelling the mechanisms involved in the switch between acute and persistent TB infections and provide a means to study aspects of this important phenomenon in vitro. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-83
Experiment types
transcription profiling by array, genetic modification, growth condition, replicate
Contact
Citation
The genetic requirements for fast and slow growth in mycobacteria. Beste DJ, Espasa M, Bonde B, Kierzek AM, Stewart GR, McFadden J. PLoS One 4(4):e5349 (2009), Europe PMC 19479006
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-BUGS-83.idf.txt
Sample and data relationshipE-BUGS-83.sdrf.txt
Raw data (1)E-BUGS-83.raw.1.zip
Processed data (1)E-BUGS-83.processed.1.zip
Experiment designE-BUGS-83.biosamples.png, E-BUGS-83.biosamples.svg
Array designsA-BUGS-1.adf.txt, A-BUGS-2.adf.txt
Links