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

@unpublished{Zeden:2017:10.1101/216887,
author = {Zeden, MS and Schuster, CF and Bowman, L and Zhong, Q and Williams, HD and Gründling, A},
doi = {10.1101/216887},
title = {Cyclic-di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in<i>Staphylococcus aureus</i>but dispensable for viability in anaerobic conditions},
url = {http://dx.doi.org/10.1101/216887},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>ABSTRACT</jats:title><jats:p>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<jats:italic>Staphylococcus aureus</jats:italic>. However, the exact role of this molecule has not been identified.<jats:italic>dacA</jats:italic>, the<jats:italic>S. aureus</jats:italic>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<jats:italic>S. aureus dacA</jats:italic>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<jats:italic>dacA</jats:italic>were identified in<jats:italic>alsT</jats:italic>and<jats:italic>opuD</jats:italic>, encoding a predicted amino acid and osmolyte transporter, the latter of which we show here to be the main glycine betaine-uptake system in<jats:italic>S. aureus</jats:italic>. 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<jats:italic>hepS, hemB, ctaA</jats:italic>and<jats:italic>qoxB</jats:italic>, coding for proteins required for respiration. Furthermore, we show that<jats:italic>dacA</jats:italic>is dispensable for growth in anaerobic conditions. Together, these finding reveal an essential role for the c-d
AU  - Zeden,MS
AU  - Schuster,CF
AU  - Bowman,L
AU  - Zhong,Q
AU  - Williams,HD
AU  - Gründling,A
DO  - 10.1101/216887
PY  - 2017///
TI  - Cyclic-di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in<i>Staphylococcus aureus</i>but dispensable for viability in anaerobic conditions
UR  - http://dx.doi.org/10.1101/216887
ER  -
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