Title |
Mycobacterium tuberculosis gene expression at different stages of hypoxia-induced dormancy and upon resuscitation |
Author |
Elisabetta Iona, Manuela Pardini, Alessandro Mustazzolu, Giovanni Piccaro, Roberto Nisini, Lanfranco Fattorini, and Federico Giannoni* |
Address |
Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy |
Bibliography |
Journal of Microbiology, 54(8),565-572, 2016,
|
DOI |
10.1007/s12275-016-6150-4
|
Key Words |
Mycobacterium tuberculosis, H37Rv, dormancy,
gene expression |
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. |