title: Mycobacterium tuberculosis gene expression at different stages of hypoxia-induced dormancy and upon resuscitation.
abstract: The physiology of dormant Mycobacterium tuberculosis was studied in detail by examining the gene expression of 51 genes using quantitative Reverse-Transcription Polymerase Chain Reaction. A forty-day period of dormancy in the Wayne culture model depicted four major transcription patterns. Some sigma factors and many metabolic genes were constant, whereas genes belonging to the dormancy regulon were activated on day 9. In particular, alpha-crystallin mRNA showed more than a 1,000-fold increase compared to replicating bacilli. Genes belonging to the enduring hypoxic response were up-regulated at day 16, notably, transcription factors sigma B and E. Early genes typical of log-phase bacilli, esat-6 and fbpB, were uniformly down-regulated during dormancy. Late stages of dormancy showed a drop in gene expression likely due to a lack of substrates in anaerobic respiration as demonstrated by the transcriptional activation observed following nitrates addition. Among genes involved in nitrate metabolism, narG was strongly up-regulated by nitrates addition. Dormant bacilli responded very rapidly when exposed to oxygen and fresh medium, showing a transcriptional activation of many genes, including resuscitation-promoting factors, within one hour. Our observations extend the current knowledge on dormant M. tuberculosis gene expression and its response to nutrients and to aerobic and anaerobic respiration.
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iona
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Pardini
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mustazzolu
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Piccaro
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Nisini
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Fattorini
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. federico.giannoni@iss.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Giannoni
mesh_terms: D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D018507:Gene Expression Regulation, Developmental; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D018085:Regulon
chemical_list: D001426:Bacterial Proteins; D010100:Oxygen
keywords: H37Rv; Mycobacterium tuberculosis; dormancy; gene expression