title: Gene expression profile of Mycobacterium tuberculosis in a non-replicating state.
abstract: Mycobacterium tuberculosis is able to persist in the human host for decades in an apparently dormant state where it is presumed to reside in an hypoxic environment. This can be mimicked by the Wayne culture model in which progressive oxygen depletion causes the bacteria to shift into a non-replicating state. We investigated global gene expression in aerobic (roller), microaerophilic (NRP1) and anaerobic (NRP2) cultures. A number of genes were significantly up-regulated as compared to aerobic culture; 178 in NRP1, 210 in NRP2, 88 in both. The two states showed distinct gene expression profiles, although a number of membrane and transmembrane proteins were induced in both conditions. A number of regulatory proteins were up-regulated in NRP2. Glycine dehydrogenase, nitrate reductase and alpha-crystallin were induced in both stages, as were fatty acid metabolism genes including fadD26 and mas and genes of the DosR regulon. In a comparison with other stress conditions, there were more similarities between anaerobic conditions and carbon starvation or heat shock than between microaerophilic conditions and carbon starvation or heat shock, but as expected microaerophilic and anaerobic conditions showed the most similar profile. Our results indicate that a large number of genes are up-regulated during the shift into the persistent state.
authors.affiliation: Centre for Infectious Disease, Institute for Cell and Molecular Science, Barts and the London, Queen Mary's School of Medicine and Dentistry, Turner Street, London E1 2AD, UK.
authors.forename: D G Niranjala
authors.initials: DG
authors.lastname: Muttucumaru
authors.forename: Gretta
authors.initials: G
authors.lastname: Roberts
authors.forename: Jason
authors.initials: J
authors.lastname: Hinds
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stabler
authors.forename: Tanya
authors.initials: T
authors.lastname: Parish
mesh_terms: D000332:Aerobiosis / Q000502:physiology; D000693:Anaerobiosis / Q000502:physiology; D001692:Biological Transport / Q000235:genetics; D002244:Carbon / Q000378:metabolism; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial; D018869:Heat-Shock Response / Q000502:physiology; D066298:In Vitro Techniques; D007522:Isocitrate Lyase / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015854:Up-Regulation
chemical_list: D004269:DNA, Bacterial; D005227:Fatty Acids; D002244:Carbon; D007522:Isocitrate Lyase