Imperial College London
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DrAndrewEdwards

Faculty of Medicine, Department of Infectious Disease

Director of Postgraduate Education & Senior Lecturer
 
 
 
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Contact

 

a.edwards Website

 
 
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Location

 

5.40AFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pader:2016:10.1038/nmicrobiol.2016.194,
author = {Pader, V and Hakim, S and Painter, KL and Wigneshweraraj, S and Clarke, TB and Edwards, A},
doi = {10.1038/nmicrobiol.2016.194},
journal = {Nature Microbiology},
pages = {1--8},
title = {Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids},
url = {http://dx.doi.org/10.1038/nmicrobiol.2016.194},
volume = {2},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA)1,2. Although resistance is rare, treatment failure can occur in more than 20% of cases3,4 and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Here, we show that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhances S. aureus survival during daptomycin treatment. Wild-type S. aureus was killed rapidly by daptomycin, but Agr-defective mutants survived antibiotic exposure by releasing membrane phospholipids, which bound and inactivated the antibiotic. Although wild-type bacteria also released phospholipid in response to daptomycin, Agr-triggered secretion of small cytolytic toxins, known as phenol soluble modulins, prevented antibiotic inactivation. Phospholipid shedding by S. aureus occurred via an active process and was inhibited by the β-lactam antibiotic oxacillin, which slowed inactivation of daptomycin and enhanced bacterial killing. In conclusion, S. aureus possesses a transient defence mechanism that protects against daptomycin, which can be compromised by Agr-triggered toxin production or an existing therapeutic antibiotic.
AU  - Pader,V
AU  - Hakim,S
AU  - Painter,KL
AU  - Wigneshweraraj,S
AU  - Clarke,TB
AU  - Edwards,A
DO  - 10.1038/nmicrobiol.2016.194
EP  - 8
PY  - 2016///
SN  - 2058-5276
SP  - 1
TI  - Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids
T2  - Nature Microbiology
UR  - http://dx.doi.org/10.1038/nmicrobiol.2016.194
UR  - https://www.nature.com/articles/nmicrobiol2016194
UR  - http://hdl.handle.net/10044/1/40119
VL  - 2
ER  -
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