Dataset Information


Effect of INH treatment on Mycobacterium tuberculosis gene expression in various dormancy models.

ABSTRACT: These data represent the expression patterns of Mycobacterium tuberculosis in progressive hypoxia, nutrient depletion, and in-vivo hollow fiber models of dormancy. The assumptions are that the set of genes that respond to INH treatment during Log phase growth would not be differentially regulated during INH treatment in the dormancy models, and that the overall number of differentially regulated genes would be reduced do to the low metabolic state of the cells. Keywords: Dormancy Model Drug Response Comparison Overall design: Each condition was repeated as multiple biological replicates to reduce the number of false positives caused by temporal and human inconsistencies. The in-vitro growth experiments represent a positive control and a core set of genes have previously been shown to respond to INH treatment under these conditions. The KatG mutant represents a negative control. In this case the drug is not converted to its active form by the catalase and thus any change in gene regulation would be caused by change in osmotic potential by the introduction of a soluble but non-metabolisable substrate. The progressive hypoxia model is similar to the KatG mutant because oxygen is required for the activity of the gene, but the overall phenotypic state of the cell is non-replicative. The nutrient depletion model is also non-replicative dormancy model in which the drug should be in its active state. The hollow fiber model model is an in-vivo model and is hypothesized to be both low nutrient and low oxygen as well as contain a variety of other stresses. This model is also marked by a different drug delivery system as it must first pass through the host. Together these models should demonstrate Mycobacterium tuberculosis gene expression under different metabolic cell states as well as different drug states.

INSTRUMENT(S): Colorado State University Mycobacterium Tuberculosis V2

SUBMITTER: Petros Karakousis  

PROVIDER: GSE9776 | GEO | 2007-12-14



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Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis.

Karakousis Petros C PC   Williams Ernest P EP   Bishai William R WR  

The Journal of antimicrobial chemotherapy 20071221 2

OBJECTIVES: Despite having potent activity against actively replicating Mycobacterium tuberculosis, isoniazid has very limited activity against dormant bacilli. In order to investigate the lack of bactericidal activity of this drug under conditions leading to mycobacterial dormancy, we studied the transcriptional pattern of M. tuberculosis in different physiological states following exposure to isoniazid. METHODS: Global gene expression analysis was used to study M. tuberculosis treated with iso  ...[more]

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