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Coupling of Peptidoglycan Synthesis to Central Metabolism in Mycobacteria: Post-transcriptional Control of CwlM by Aconitase

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journal contribution
posted on 30.10.2020, 10:19 by Peter J Bancroft, Obolbek Turapov, Heena Jagatia, Kristine B Arnvig, Galina V Mukamolova, Jeffrey Green
Mycobacterium tuberculosis causes human tuberculosis, and a better understanding of its biology is required to identify vulnerabilities that might be exploited in developing new therapeutics. The iron-sulfur cluster of the essential M. tuberculosis central metabolic enzyme, aconitase (AcnA), disassembles when exposed to oxidative/nitrosative stress or iron chelators. The catalytically inactive apo-AcnA interacts with a sequence resembling an iron-responsive element (IRE) located within the transcript of another essential protein, CwlM, a regulator of peptidoglycan synthesis. A Mycobacterium smegmatis cwlM conditional mutant complemented with M. tuberculosis cwlM with a disrupted IRE is unable to recover from combinations of oxidative, nitrosative, and iron starvation stresses. An equivalent M. tuberculosis cwlM conditional mutant complemented with the cwlM gene lacking a functional IRE exhibits a growth defect in THP-1 macrophages. It appears that AcnA acts to couple peptidoglycan synthesis and central metabolism, and disruption of this coupling potentially leaves mycobacteria vulnerable to attack by macrophages.

History

Citation

Cell Reports, Volume 32, Issue 13, 29 September 2020, 108209

Author affiliation

Department of Respiratory Sciences, University of Leicester

Version

VoR (Version of Record)

Published in

Cell Reports

Volume

32

Issue

13

Pagination

108209 - 108209

Publisher

Elsevier BV

issn

2211-1247

Acceptance date

09/09/2020

Copyright date

2020

Available date

29/09/2020

Language

en