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Sci Signal. 2016 Aug 16;9(441):ra81. doi: 10.1126/scisignal.aaf7279.

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

Author information

1
Section of Microbiology and MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK.
2
Section of Structural Biology, Department of Medicine, Imperial College London, London SW7 2AZ, UK.
#
Contributed equally

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.

PMID:
27531650
PMCID:
PMC5248971
DOI:
10.1126/scisignal.aaf7279
[Indexed for MEDLINE]
Free PMC Article

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