Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling by array of Rifampicin-induced transcriptome response in rifampicin-resistant Mycobacterium tuberculosis


ABSTRACT: Tuberculosis (TB) is still a major life-threatening infectious disease, within which especially the rise of multidrug resistant TB (MDR-TB) is currently worrying. This study focuses on mechanisms of development of rifampicin resistance, since rifampicin seems to play an important role in the development of MDR-TB. To provide further insight in rifampicin resistance, we performed a genome-wide transcriptional profile analysis for Mycobacterium tuberculosis (M. tuberculosis) using microarray technology and qRT-PCR analysis. We exposed a rifampicin-susceptible H37Rv wild type (H37Rv-WT) and a rifampicin-resistant progeny H37Rv strain with a H526Y mutation in the rpoB gene (H37Rv-H526Y) to several concentrations of rifampicin, to define the effect of rifampicin on the transcription profile. Our study showed that there are resistance-dependant differences in response between both M. tuberculosis strains. Gene clusters associated with efflux, transport and virulence were altered in the rifampicin-resistant H37Rv mutant compared to the rifampicin-susceptible H37Rv-WT strain after exposure to rifampicin. We conclude that the small gene cluster Rv0559c-Rv0560c in the H37Rv-H526Y strain was remarkably up-regulated in the microarray analysis and qRT-PCR results and appeared to be dependent on rifampicin concentration and time of exposure. Therefore this study suggests that Rv0559c and Rv0560c play a pivotal role in rifampicin resistance of M. tuberculosis. Further investigation of Rv0559c and Rv0560c is needed to reveal function and mechanism of both genes that were triggered upon rifampicin exposure. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-139]

ORGANISM(S): Mycobacterium tuberculosis

SUBMITTER: Adam Witney 

PROVIDER: E-BUGS-139 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Rifampicin-induced transcriptome response in rifampicin-resistant Mycobacterium tuberculosis.

de Knegt Gerjo J GJ   Bruning Oskar O   ten Kate Marian T MT   de Jong Mark M   van Belkum Alex A   Endtz Hubert P HP   Breit Timo M TM   Bakker-Woudenberg Irma A J M IA   de Steenwinkel Jurriaan E M JE  

Tuberculosis (Edinburgh, Scotland) 20121122 1


Tuberculosis (TB) is still a major life-threatening infectious disease, within which especially the rise of multidrug resistant TB (MDR-TB) is currently worrying. This study focuses on mechanisms of development of rifampicin resistance, since rifampicin seems to play an important role in the development of MDR-TB. To provide further insight in rifampicin resistance, we performed a genome-wide transcriptional profile analysis for Mycobacterium tuberculosis (M. tuberculosis) using microarray techn  ...[more]

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