E-GEOD-8839 - Inhibition of Respiration by Nitric Oxide Induces a Mycobacterium tuberculosis Dormancy Program

Status
Released on 21 August 2007, last updated on 2 May 2014
Organism
Mycobacterium tuberculosis
Samples (262)
Arrays (2)
Protocols (8)
Description
An estimated two billion persons are latently infected with Mycobacterium tuberculosis. The host factors that initiate and maintain this latent state and the mechanisms by which M. tuberculosis survives within latent lesions are compelling but unanswered questions. One such host factor may be nitric oxide (NO), a product of activated macrophages that exhibits antimycobacterial properties. Evidence for the possible significance of NO comes from murine models of tuberculosis showing progressive infection in animals unable to produce the inducible isoform of NO synthase and in animals treated with a NO synthase inhibitor. Here, we show that O2 and low, nontoxic concentrations of NO competitively modulate the expression of a 48-gene regulon, which is expressed in vivo and prepares bacilli for survival during long periods of in vitro dormancy. NO was found to reversibly inhibit aerobic respiration and growth. A heme-containing enzyme, possibly the terminal oxidase in the respiratory pathway, likely senses and integrates NO and O2 levels and signals the regulon. These data lead to a model postulating that, within granulomas, inhibition of respiration by NO production and O2 limitation constrains M. tuberculosis replication rates in persons with latent tuberculosis. The quality controls were biological replicate and technical replicate
Experiment type
transcription profiling by array 
Contacts
SMD Staff <array@genome.stanford.edu>, Dirk Schnappinger, Kevin C Visconti, Martin I Voskuil
Citation
Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. Voskuil MI, Schnappinger D, Visconti KC, Harrell MI, Dolganov GM, Sherman DR, Schoolnik GK. , Europe PMC 12953092
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-8839.idf.txt
Sample and data relationshipE-GEOD-8839.sdrf.txt
Raw data (1)E-GEOD-8839.raw.1.zip
Processed data (1)E-GEOD-8839.processed.1.zip
Array designsA-GEOD-8561.adf.txt, A-GEOD-9901.adf.txt
Links