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{Zeden:2018:10.1074/jbc.M117.818716,
author = {Zeden, MS and Schuster, CF and Bowman, L and Zhong, Q and Williams, HD and Grundling, A},
doi = {10.1074/jbc.M117.818716},
journal = {Journal of Biological Chemistry},
pages = {3180--3200},
title = {Cyclic-di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in Staphylococcus aureus but dispensable for viability in anaerobic conditions},
url = {http://dx.doi.org/10.1074/jbc.M117.818716},
volume = {293},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered signaling molecule important for the survival of Firmicutes, a large bacterial group that includes notable pathogens such as Staphylococcus aureus. However, the exact role of this molecule has not been identified. dacA, the S. aureus gene encoding the diadenylate cyclase enzyme required for c-di-AMP production, cannot be deleted when bacterial cells are grown in rich medium, indicating that c-di-AMP is required for growth in this condition. Here, we report that an S. aureus dacA mutant can be generated in chemically defined medium. Consistent with previous findings, this mutant had a severe growth defect when cultured in rich medium. Using this growth defect in rich medium, we selected for suppressor strains with improved growth to identify c-di-AMP-requiring pathways. Mutations bypassing the essentiality of dacA were identified in alsT and opuD, encoding a predicted amino acid and osmolyte transporter, the latter of which we show here to be the main glycine betaine-uptake system in S. aureus. Inactivation of these transporters likely prevents the excessive osmolyte and amino acid accumulation in the cell, providing further evidence for a key role of c-di-AMP in osmotic regulation. Suppressor mutations were also obtained in hepS, hemB, ctaA and qoxB, coding for proteins required for respiration. Furthermore, we show that dacA is dispensable for growth in anaerobic conditions. Together, these finding reveal an essential role for the c-di-AMP signaling network in aerobic, but not anaerobic, respiration in S. aureus.
AU  - Zeden,MS
AU  - Schuster,CF
AU  - Bowman,L
AU  - Zhong,Q
AU  - Williams,HD
AU  - Grundling,A
DO  - 10.1074/jbc.M117.818716
EP  - 3200
PY  - 2018///
SN  - 0021-9258
SP  - 3180
TI  - Cyclic-di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in Staphylococcus aureus but dispensable for viability in anaerobic conditions
T2  - Journal of Biological Chemistry
UR  - http://dx.doi.org/10.1074/jbc.M117.818716
UR  - https://www.sciencedirect.com/science/article/pii/S0021925820390554?via%3Dihub
UR  - http://hdl.handle.net/10044/1/56750
VL  - 293
ER  -
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