Overexpression of the Rv0805 phosphodiesterase elicits a cAMP-independent transcriptional response

Matange, Nishad and Hunt, Debbie M and Buxton, Roger S and Visweswariah, Sandhya S (2013) Overexpression of the Rv0805 phosphodiesterase elicits a cAMP-independent transcriptional response. In: Tuberculosis, 93 (5). pp. 492-500.

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Abstract

The Rv0805 gene in Mycobacterium tuberculosis encodes a metallophosphoesterase which shows cAMP-hydrolytic activity. Overexpression of Rv0805 has been used as a tool to lower intracellular cAMP levels and thereby elucidate the roles of cAMP in mycobacteria. Here we show that levels of cAMP in M. tuberculosis were lowered by only similar to 30% following overexpression of Rv0805, and transcript levels of a number of genes, which include those associated with virulence and the methyl citrate cycle, were altered. The genes that showed altered expression were distinct from those differentially regulated in a strain deleted for the cAMP-receptor protein (CRPMt), consistent with the relatively low dependence on cAMP of CRPMt binding to DNA. Using mutants of Rv0805 we show that the transcriptional signature of Rv0805 overexpression is a combination of catalysis-dependent and independent effects, and that the structurally flexible C-terminus of Rv0805 is crucial for the catalysis-independent effects of the protein. Our study demonstrates the dissociation of Rv0805 and cAMP-regulated gene expression, and reveals alternate functions for this phosphodiesterase from M. tuberculosis.

Item Type:	Journal Article
Publication:	Tuberculosis
Publisher:	Churchill Livingstone
Additional Information:	Copyright of this article belongs to Churchill Livingstone.
Keywords:	Cyclic AMP; Phosphodiesterase; Microarray; Rv0805; Mycobacterium Tuberculosis
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	26 Sep 2013 05:35
Last Modified:	26 Sep 2013 05:35
URI:	http://eprints.iisc.ac.in/id/eprint/47430

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