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The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus

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Title: The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus
Author(s): Grundling, A
Schuster, C
Bellows, L
Tosi, T
Campeotto
Corrigan
Freemont, P
Item Type: Journal Article
Abstract: Staphylococcus aureus is an important opportunistic human pathogen that is highly resistant to osmotic stresses. To survive an increase in osmolarity, bacteria immediately take up potassium ions and small organic compounds known as compatible solutes. The second messenger cyclic diadenosine monophosphate (c-di-AMP) reduces the ability of bacteria to withstand osmotic stress by binding to and inhibiting several proteins that promote potassium uptake. We identified OpuCA, the adenosine triphosphatase (ATPase) component of an uptake system for the compatible solute carnitine, as a c-di-AMP target protein in S. aureus and found that the LAC*ΔgdpP strain of S. aureus, which overproduces c-di-AMP, showed reduced carnitine uptake. The paired cystathionine-β-synthase (CBS) domains of OpuCA bound to c-di-AMP, and a crystal structure revealed a putative binding pocket for c-di-AMP in the cleft between the two CBS domains. Thus, c-di-AMP inhibits osmoprotection through multiple mechanisms.
Publication Date: 16-Aug-2016
Date of Acceptance: 20-Jul-2016
URI: http://hdl.handle.net/10044/1/39084
DOI: http://dx.doi.org/10.1126/scisignal.aaf7279
ISSN: 1945-0877
Publisher: American Association for the Advancement of Science
Start Page: ra81
End Page: ra81
Journal / Book Title: Science Signaling
Volume: 9
Issue: 441
Copyright Statement: This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Signaling on Sci. Signal. 16 Aug 2016, DOI: http://dx.doi.org/10.1126/scisignal.aaf7279.
Sponsor/Funder: Commission of the European Communities
Wellcome Trust
Funder's Grant Number: 260371
100289/Z/12/Z
Keywords: 0601 Biochemistry And Cell Biology
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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