Unknown,Transcriptomics,Genomics,Proteomics

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In vitro dormancy achieved by multiple stresses in Mycobacterium tuberculosis

ABSTRACT: The human pathogen, Mycobacterium tuberculosis, develops a dormant infection, in which organisms survive within the body. We established a unique in vitro dormancy model based on the characterization of drug-resistance to INH and rifampin. M. tuberculosis cells were maintained in controlled and defined multiple stress conditions with low oxygen (5% dissolved oxygen tension), acid (pH 5.) along with glycerol-deprived medium conditions. To monitor gene expression changes in M. tuberculosis in response to the multiple stresses, we performed microarray analysis at the time point of 1, 2, 3, 6, and 12days after treatment. M. tuberculosis adapting to multiple stresses displayed characteristics associated with persistence in vivo, including entry into a non-replicative state and the repression of genes involved in energy regeneration. Under in vitro multiple-stresses, M. tuberculosis significantly modulated gene expression mainly in response to the starvation stresses. Cells exposed to these multiple stress conditions shows significant drug-resistance. Comparison with other in vivo expression profiles demonstrates induction of several common genes for in vitro dormancy conditions. Keywords: Stress response in time course. Samples under multiple stress condition were taken at day 1, 2, 3, 6, and 12 for microarray hybridization. More than two technical replicates per biological samples with Cy3/5 dye-swaps.

ORGANISM(S): Mycobacterium tuberculosis H37Rv

SUBMITTER: ChangMuk Lee

PROVIDER: E-GEOD-10391 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen.

Deb Chirajyoti C Lee Chang-Muk CM Dubey Vinod S VS Daniel Jaiyanth J Abomoelak Bassam B Sirakova Tatiana D TD Pawar Santosh S Rogers Linda L Kolattukudy Pappachan E PE

PloS one 20090629 6

<h4>Background</h4>Mycobacterium tuberculosis (Mtb) becomes dormant and phenotypically drug resistant when it encounters multiple stresses within the host. Inability of currently available drugs to kill latent Mtb is a major impediment to curing and possibly eradicating tuberculosis (TB). Most in vitro dormancy models, using single stress factors, fail to generate a truly dormant Mtb population. An in vitro model that generates truly dormant Mtb cells is needed to elucidate the metabolic require ...[more]

PMID: 19562030

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Dataset Information

In vitro dormancy achieved by multiple stresses in Mycobacterium tuberculosis

Publications

A novel in vitro multiple-stress dormancy model for Mycobacterium tuberculosis generates a lipid-loaded, drug-tolerant, dormant pathogen.

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