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The transcriptome as a bioprobe of the Mtb intracellular environment.

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posted on 21.06.2012, 00:23 by Kyle H. Rohde, Diogo F. T. Veiga, Shannon Caldwell, Gábor Balázsi, David G. Russell

Gene trees of select signature genesets that are useful as surrogate readouts of the conditions encountered by Mtb within macrophages. (A) Hypoxia/RNI/CO. Genes of the well-characterized dosRS-dependent “dormancy” regulon [29] indicate exposure of Mtb to known cues of this geneset (hypoxia, reactive nitrogen intermediates (RNI), and carbon monoxide (CO)). (B) “Guilt by association” analysis. Genes regulated in synch with known virulence regulons – i.e. the DosR regulon - were identified by using a highly regulated member of this regulon, hspX, in place of synthetic profiles. (C) Acid Stress. Select members of a regulon activated by acidic pH in vitro and within macrophage phagosomes [12] report on the pH encountered by Mtb within its vacuole.