Overexpression of the Rv0805 Phosphodiesterase Elicits a CAMP-independent Transcriptional Response

Overview

Journal Tuberculosis (Edinb)

Specialties Infectious Diseases
Pulmonary Medicine

Date 2013 Jul 10

PMID 23835087

Citations 7

Authors

Nishad Matange

Debbie M Hunt

Roger S Buxton

Sandhya S Visweswariah

Affiliations

Soon will be listed here.

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 ∼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 (CRP(Mt)), consistent with the relatively low dependence on cAMP of CRP(Mt) 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.

Citing Articles

PhoP integrates stress response to intracellular survival by regulating cAMP level.

Khan H, Paul P, Goar H, Bamniya B, Baid N, Sarkar D Elife. 2024; 13.

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Mycobacterial phosphodiesterase Rv0805 is a virulence determinant and its cyclic nucleotide hydrolytic activity is required for propionate detoxification.

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Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall-targeting antimicrobials.

Thomson M, Liu Y, Nunta K, Cheyne A, Fernandes N, Williams R J Biol Chem. 2022; 298(8):102151.

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Cyclic nucleotide signaling in Mycobacterium tuberculosis: an expanding repertoire.

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Eukaryotic-Type Ser/Thr Protein Kinase Mediated Phosphorylation of Mycobacterial Phosphodiesterase Affects its Localization to the Cell Wall.

Malhotra N, Chakraborti P Front Microbiol. 2016; 7:123.

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