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.
journal_name
Sci Signaljournal_title
Science signalingauthors
Schuster CF,Bellows LE,Tosi T,Campeotto I,Corrigan RM,Freemont P,Gründling Adoi
10.1126/scisignal.aaf7279subject
Has Abstractpub_date
2016-08-16 00:00:00pages
ra81issue
441eissn
1945-0877issn
1937-9145journal_volume
9pub_type
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