Imperial College London
Alternate

Professor Angelika Gründling

Faculty of Medicine, Department of Infectious Disease

Professor of Molecular Microbiology
 
 
 
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Contact

 

+44 (0)20 7594 5256a.grundling Website

 
 
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Location

 

6.22Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bowman:2016:10.1074/jbc.M116.747709,
author = {Bowman, L and Zeden, MS and Schuster, CF and Kaever, V and Grundling, A},
doi = {10.1074/jbc.M116.747709},
journal = {Journal of Biological Chemistry},
pages = {26970--26986},
title = {New Insights into the Cyclic di-Adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic-Dinucleotide for Acid Stress Resistance in Staphylococcus aureus.},
url = {http://dx.doi.org/10.1074/jbc.M116.747709},
volume = {291},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane bound Asp-His-His and Asp-His-His associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared to the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus, but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism.
AU  - Bowman,L
AU  - Zeden,MS
AU  - Schuster,CF
AU  - Kaever,V
AU  - Grundling,A
DO  - 10.1074/jbc.M116.747709
EP  - 26986
PY  - 2016///
SN  - 1083-351X
SP  - 26970
TI  - New Insights into the Cyclic di-Adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic-Dinucleotide for Acid Stress Resistance in Staphylococcus aureus.
T2  - Journal of Biological Chemistry
UR  - http://dx.doi.org/10.1074/jbc.M116.747709
UR  - http://www.ncbi.nlm.nih.gov/pubmed/27834680
UR  - http://hdl.handle.net/10044/1/42555
VL  - 291
ER  -
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